Methods  Surgeons prospectively enrolled patients with nonneovascular AMD who were awaiting cataract surgery. Fluorescein angiography was performed preoperatively and at the postoperative week 1, month 3, and month 12 visits. Incidence of neovascular AMD development within 12 months after operation was the primary outcome measure.

Results  A total of 108 subjects were enrolled. Of 86 eyes with preoperatively photographically confirmed nonneovascular AMD, 71 had gradable images by month 12. Neovascular AMD was observed in 9 of 71 eyes (12.7%; 95% confidence interval, 6.0%-22.7%). The progression rate between week 1 and month 12 decreased to 3 of 65 eyes (4.6%; 95% confidence interval, 1.0%-12.9%) after excluding 5 neovascular events identified on the postoperative week 1 visit and 1 case with missing photographs at this visit.

Conclusion  The low incidence rate of neovascular AMD development between 1 week and 1 year after cataract surgery did not support the hypothesis that cataract surgery increases the risk of AMD progression. Several eyes appeared to have disease progression on postsurgery week 1 fluorescein angiograms, suggesting that many cases of presumed progression to neovascular AMD following cataract surgery may have been present prior to cataract surgery, but not recognized owing to lens opacity.

Methods  Twenty-nine eyes (16 patients) received myopic LASIK or PRK, with intended correction to emmetropia. Central endothelial photographs were taken before and 9 years after surgery and were analyzed by the same masked investigator after appropriate calibration for magnification. Comparisons were made by using generalized estimating equation models to account for any correlation between fellow eyes of the same patient. The annual exponential rate of cell loss was compared with cell loss during a 10-year period in 42 normal (unoperated) corneas of 42 subjects.

Results  Endothelial cell density 9 years after LASIK and PRK had decreased by 5.3% from preoperative density (P < .001), whereas coefficient of variation of cell area (P = .24) and percentage of hexagonal cells (P = .19) did not change. The mean annual rate of cell loss after refractive surgery (0.6% [standard deviation, 0.8%]) was not different from that in normal corneas (0.6% [0.5%], P = .88; minimum detectable difference = 0.5%;  = .05; β = .20).

Conclusions  Laser in situ keratomileusis and PRK had no long-term effect on the corneal endothelium. Corneas that have undergone LASIK or PRK can be considered for use as donors for posterior lamellar keratoplasty procedures.

Methods  Scores of such risks as infrequent blinking, blink-related microtrauma, conjunctival inflammation, elevated intraocular pressure, dry eye, symblepharon, lagophthalmos, and previous KLAL or penetrating keratoplasty (PKP) failure were calculated and recorded before, during, and after KLAL. Prolonged oral mycophenolate mofetil and tacrolimus and short-term prednisone and acyclovir were administered in 12 eyes (10 consecutive patients) with total limbal stem cell deficiency after KLAL. Ten eyes underwent subsequent PKP.

Results  More corrective measures were required in eyes with higher risk scores. During a follow-up of 61.2 months (standard deviation [SD], 18.2; range, 36-91 months) after KLAL, postoperative epithelial breakdown due to exposure occurred late in the period after PKP and remained a primary risk. Mean daily doses of 1.4 g of mycophenolate mofetil and 1.6 mg of tacrolimus were administered for 52.7 months (SD, 22.5; range, 23-91 months) with few adverse effects and reached trough levels of 1.6 µg/mL (SD, 0.6 µg/mL) and 4.5 ng/mL (SD, 2 ng/mL), respectively. Keratolimbal allograft and PKP rejection was noted in 2 and 3 eyes, respectively, though there was a reversal in 1 eye in each group, yielding final KLAL and PKP survivals in 10 and 8 eyes, respectively, and ambulatory visual acuity of up to 20/20 in 10 eyes for 67.2% of the entire follow-up period.

Conclusion  Correction of ocular surface deficits combined with an immunosuppressive regimen further improves the long-term outcome of KLAL in eyes with total limbal stem cell deficiency.

Methods  The medical records of patients with primary congenital glaucoma who underwent AGV implantation with a minimum follow-up of 6 months were reviewed. The primary outcome measure was cumulative probability of success, defined as intraocular pressure greater than 5 mm Hg and less than 23 mm Hg and at least a 15% reduction from the preoperative intraocular pressure, without serious complications, additional glaucoma surgery, or loss of light perception.

Results  Thirty eyes of 19 children with primary congenital glaucoma who underwent AGV implantation with a minimum follow-up of 6 months were reviewed. The children had a mean (SD) age of 1.8 (2.6) years, a mean (SD) preoperative intraocular pressure of 28.4 (6.7) mm Hg, and a mean (SD) follow-up time of 57.6 (48.0) months. The cumulative probability of success was 63% in 1 year and 33% in 5 years. After a second AGV implantation, the cumulative probability of success was 86% in 1 and 2 years and 69% in 5 years. Hispanic ethnicity (P = .02) and being female (P = .005) were associated with increased risk of failure.

Conclusions  Thirty-three percent of AGV implantations in children with primary congenital glaucoma were successful after 5 years of follow-up. With the implantation of a second AGV, the 5-year success rate increased to 69%.

Methods  One randomly selected eye of each subject underwent standard automated perimetry, stereoscopic photography, scanning laser polarimetry with enhanced corneal compensation, and time-domain and spectral-domain optical coherence tomography (OCT). Mean retinal sensitivity values were calculated in the normal standard automated perimetry hemifield of the glaucoma group and randomly selected hemifields in the normal and suspected glaucoma groups. The mean RNFL thickness values corresponding to the normal hemifield were calculated. Glaucoma severity was judged using standard automated perimetry pattern standard deviation and the Heidelberg retina tomograph–derived linear cup-disc ratio.

Results  Fifty subjects were enrolled in each group. Mean RNFL thickness in the normal hemifield obtained using spectral-domain OCT, time-domain OCT, and scanning laser polarimetry with enhanced corneal compensation was significantly (P ≤ .01) thinner in the glaucoma group compared with the normal and suspected glaucoma groups. Mean retinal sensitivity in the normal hemifield was significantly (P < .001) reduced in the glaucoma group compared with the normal and suspected glaucoma groups. The Heidelberg retina tomograph–derived cup-disc ratio was significantly correlated with mean RNFL thickness in the normal hemifield obtained using spectral-domain OCT, time-domain OCT, and scanning laser polarimetry with enhanced corneal compensation (P ≤ .01).

Conclusions  Diffuse RNFL atrophy and retinal sensitivity loss exist in glaucomatous eyes with localized standard automated perimetry deficits. Glaucomatous damage affects both structure and function in a linear proportion.

Methods  Extended family members of the proband underwent dilated fundus examination, optical coherence tomography, and, in selected cases, fluorescein angiography and electroretinography.

Results  Seventeen family members, representing 3 generations and ranging in age from 5 to 64 years, were clinically examined. Visual acuities ranged from 20/20 to 20/200. Amblyopia and strabismus were frequently present in affected individuals. Consistent with an autosomal dominant pattern of inheritance, 7 family members had multiple central macular cystic spaces and flat, round, densely pigmented spots within the retina. There were right-angle vessels and telangiectasis in the central macula. Two subjects showed evidence of active macular neovascularization with leakage on fluorescein angiography at ages 7 and 24 years, which was responsive to either focal laser or a single injection of bevacizumab. In those cases examined, multifocal electroretinography showed a diminished foveal response.

Conclusions  This spotted cystic neovascular macular dystrophy appears to represent a new autosomal dominant retinal condition. Because these patients are at risk for choroidal neovascularization, identification of the responsible gene may provide insight into the mechanisms of pathological neovascularization.

Methods  Optical coherence tomograms were taken at clinical sites with the Stratus OCT using fast macular and crosshair scan protocols. Paper prints of images were evaluated at a central reading center. Quality evaluation identified the accuracy of OCT-measured retinal thickness data and was categorized as good, fair, borderline, or ungradable. Manual measurement of center point thickness was performed on borderline images. Morphological evaluation identified cystoid spaces, subretinal fluid, and vitreoretinal interface abnormalities. Reproducibility of grading was assessed through formal quality control exercises.

Results  A randomly selected set of 106 images was identified for quality control. The first 2 annual regrades showed 91% and 89% intergrader agreement for OCT quality. Intraclass correlation for manually measured center point thickness was 0.99 per year. For morphological variables, intergrader agreement for cystoid spaces was 83% and 76%. Reproducibility for subretinal fluid and vitreoretinal interface abnormalities could not be interpreted owing to their limited presence in the sample.

Conclusion  Optical coherence tomogram evaluation procedures used in the SCORE Study are reproducible and can be used for multicenter longitudinal studies of retinal vein occlusion.

Methods  Type 1 diabetes was induced with streptozotocin in rats. Tear production was measured by the Schirmer test, and corneal sensitivity, by an esthesiometer. Eye drops of 10^–5M NTX or sterile vehicle were administered either once only or 4 times a day for 1 or 5 days; a single drop of insulin (1 U) was given once only.

Results  Dry eye and corneal insensitivity were detected in the diabetic rats beginning 5 weeks after streptozotocin injection. One drop of NTX or 4 times a day for 1 or 5 days reestablished tear production and corneal sensitivity within 1 hour of administration. The reversal of dry eye lasted for up to 2 to 3 days depending on drug regimen, but restitution of corneal sensation lasted for 4 to 7 days. Topical application of 1 eye drop of insulin restored corneal sensitivity within 1 hour and lasted for at least 2 days. In contrast, 1 eye drop of insulin did not increase tear production at 1, 24, or 48 hours compared with diabetic animals receiving sterile vehicle.

Conclusion  Topical treatment with NTX normalizes tear production and corneal sensitivity in type 1 diabetic rats.

Clinical Relevance  Topical application of NTX to the ocular surface may serve as an important strategy for treating dry eye and corneal anesthesia in diabetes. Its effect, if any, in other forms of decreased corneal sensitivity and/or dry eye should be investigated.

Methods  Retinal detachment was induced in mice by subretinal injection of sodium hyaluronate, 1.4%. In 1 experiment, mice received daily injections of minocycline (group 1) or saline (group 2). In a second experiment, mice were treated with minocycline or saline beginning 24 hours prior, immediately after, or 24 hours after experimental RD. In both experiments, photoreceptor cell survival and apoptosis were assessed by immunohistochemistry with primary antibodies against photoreceptor cell markers, rod rhodopsin, and cone opsin, and by terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling.

Results  Photoreceptor cell apoptosis was detected at day 1 after experimental RD, with apoptotic cells peaking in number at day 3 and dropping by day 7. Treatment with minocycline significantly reduced the number of apoptotic photoreceptor cells associated with RD when given 24 hours before or even 24 hours after RD.

Conclusions  Our data suggest that minocycline may be useful in the treatment of photoreceptor degeneration associated with RD, even when given up to 24 hours after RD.

Clinical Relevance  Use of minocycline in patients with macula-off RD may prevent photoreceptor apoptosis and glial cell proliferation, improving final visual outcomes.

Design  Women aged 50 to 79 years with high and low lutein intake from 3 sites of the Women's Health Initiative Observational Study were recruited into the Carotenoids in Age-Related Eye Disease Study. Fat intake from 1994 through 1998 was estimated using food frequency questionnaires, and AMD was assessed photographically from 2001 through 2004.

Results  Intakes of -6 and -3 polyunsaturated fatty acids, which were highly correlated (r = 0.8), were associated with approximately 2-fold higher prevalence of intermediate AMD in high vs low quintiles. However, monounsaturated fatty acid intake was associated with lower prevalence. Age interactions were often observed. In women younger than 75 years (n = 1325), total fat and saturated fatty acid intakes were associated with increased prevalence of AMD (multivariate adjusted odds ratios [95% confidence interval] for intermediate AMD, 1.7 [1.0-2.7] for quintile 5 vs quintile 1 for total fat [P = .10 for trend] and 1.6 [0.7-3.6] for saturated fatty acids [P = .23 for trend]). The associations were reversed in older women.

Conclusions  These results support a growing body of evidence suggesting that diets high in several types of fat may contribute to the risk of intermediate AMD and that diets high in monounsaturated fatty acids may be protective.

Methods  We assessed 426 individuals without PDR at baseline (213 men; 213 women) from the Pittsburgh Epidemiology of Diabetes Complications Study, an 18-year prospective cohort study of childhood-onset type 1 diabetes. Presence of PDR was determined by stereo fundus photography. Cox proportional hazards modeling with stepwise regression was used to determine the independent association of HGB level with PDR. Analyses were sex specific.

Results  There were 206 events. Although the incidence of PDR did not vary by sex (48% in both men and women), in men, HGB exhibited a positive linear relationship with 18-year incidence of PDR (hazard ratio, 1.33; 95% confidence interval, 1.10-1.60; P = .003), while in women, HGB level exhibited a quadratic relationship with PDR (P < .001). After multivariable adjustment for univariately significant covariates, HGB level remained significantly predictive of PDR in both men (P = .004) and women (P = .04).

Conclusion  Higher HGB level predicts the incidence of PDR in type 1 diabetes mellitus, though the association varies by sex, being linear and positive in men and quadratic in women.

Design  A retrospective cohort study was performed on retinoblastoma survivors who received the diagnosis from 1914 to 1984 and were interviewed in 2000. Lens doses were estimated from radiotherapy records. The cumulative time interval to cataract extraction between dose groups was compared using the log-rank test and Cox regression.

Results  Seven hundred fifty-three subjects (828 eyes) were available for analysis for an average of 32 years of follow-up. During this period, 51 cataract extractions were reported. One extraction was reported in an eye with no radiotherapy compared with 36 extractions in 306 eyes with 1 course of radiotherapy and 14 among 38 eyes with 2 or 3 treatments. The average time interval to cataract extraction in irradiated eyes was 51 years (95% confidence interval [CI], 48-54) following 1 treatment and 32 years (95% CI, 27-37) after 2 or 3 treatments. Eyes exposed to a therapeutic radiation dose of 5 Gy or more had a 6-fold increased risk (95% CI, 1.3-27.2) of cataract extraction compared with eyes exposed to 2.5 Gy or less.

Conclusions  The results emphasize the importance of ophthalmologic examination of retinoblastoma survivors who have undergone radiotherapy. The risk of cataract extraction in untreated eyes with retinoblastoma is comparable with the risk of the general population.

Methods  A total of 439 participants in the Surgery for Trichiasis, Antibiotics to Prevent Recurrence (STAR) trial had visual and subjective concerns measured before and 6 months after surgery. Trichiasis surgery was performed in at least 1 eye by integrated eye care workers. Visual acuity was measured using illiterate E versions of Early Treatment Diabetic Retinopathy Study charts with standardized, forced-choice procedures. Improvement was defined as improvement in visual acuity greater than 1 line (5 letters).

Results  The mean improvement in visual acuity for the eyes that had surgery was 0.129 logMAR units (P < .001). Surgery was associated with improvement in visual acuity compared with no surgery (odds ratio, 1.68; 95% confidence interval, 1.04-2.70). Independent predictors of visual acuity improvement in the eyes that had surgery included the number of lashes touching the globe prior to surgery and baseline visual acuity. Among patients, 93.8% described significant pain and 90.4% significant photophobia at baseline compared with only 1.4% and 0.9%, respectively, following surgery.

Conclusions  Surgery to correct trichiasis appears to provide significant visual acuity improvement as well as a decrease in subjective concerns in patients with trachomatous trichiasis.

Trial Registration  clinicaltrials.gov Identifier: NCT00347776

Methods  Genomic DNA samples derived from venous blood were collected from all family members. Complete sequencing of COL2A1 was performed on a proband. Primers for polymerase chain reaction and sequencing were designed to cover all exon and intron-exon boundaries. Direct sequencing of CSPG2 was performed on all family member samples.

Results  No detectable COL2A1 mutations were noted, making the diagnosis of ocular Stickler syndrome highly unlikely for this family. A unique base pair substitution (c.9265 + 1G>T) in intron 8 of the CSPG2 gene cosegregating with disease status was identified. This mutation occurred in a highly conserved previously reported splice site with a similar base pair substitution (G>A). Direct sequencing of this splice site mutation in 107 unrelated external controls revealed no variants, supporting the rarity of this base pair change and its causation in Wagner syndrome. This novel base pair substitution is thought to cause the deletion of exon 8 and formation of a truncated protein product.

Conclusion  Mutation screening of CSPG2 in autosomal dominant vitreoretinopathy families is important for accurate diagnosis.

Clinical Relevance  This study underscores the importance of obtaining extensive pedigree information and comparative ophthalmologic clinical information, as the phenotypic findings may vary greatly among independent family members. The study also affirms the paradigm shift from diagnosis assignment based on eponyms to that based on gene mutation type.

Methods  Analysis and correlation of the 2006 Florida Agency of Health Care Administration ED and inpatient data sets with the 2007 Florida Physician Workforce Survey.

Results  The Florida Physician Workforce Survey showed 46.3% of ophthalmologists surveyed took ED call in Florida in 2006. Based on estimates derived from the survey, 462 to 532 ophthalmologists participated in ED coverage that year. The level of workload varied considerably depending on International Classification of Diseases code diagnosis. Annual workload for open wounds to the eye, on average, ranged from 2.7 to 3.1 per ophthalmologist taking ED call.

Conclusions  Strategic planning for the delivery of ED eye care needs to consider both the number and types of cases presenting to the ED and the availability of ophthalmologists to provide care that other specialists cannot. This preliminary study explores the use of a workload statistic that may help to gauge manpower needs in the future.

Methods  The study included 639 eyes of 407 patients with suspected glaucoma followed up for an average of 8.0 years with annual standard automated perimetry visual field and optic disc stereophotographs. All patients had normal and reliable standard automated perimetry results at baseline. Conversion to glaucoma was defined as development of 3 consecutive abnormal visual fields during follow-up. Presence of progressive optic disc damage was evaluated by grading longitudinally acquired simultaneous stereophotographs. Other predictive factors included age, intraocular pressure, central corneal thickness, pattern standard deviation, and baseline stereophotograph grading. Hazard ratios for predicting visual field loss were obtained by extended Cox models, with optic disc progression as a time-dependent covariate. Predictive accuracy was evaluated using a modified R² index.

Results  Progressive optic disc damage had a hazard ratio of 25.8 (95% confidence interval, 16.0-41.7) and was the most important risk factor for development of visual field loss with an R² of 79%. The R²s for other predictive factors ranged from 6% to 26%.

Conclusions  Presence of progressive optic disc damage on stereophotographs was a highly predictive factor for future development of functional loss in glaucoma. These findings suggest the importance of careful monitoring of the optic disc appearance and a potential role for longitudinal assessment of the optic disc as an end point in clinical trials and as a reference for evaluation of diagnostic tests in glaucoma.

Methods  Prospective, nonrandomized single-center clinical study involving 28 eyes. Main outcome measures included uncorrected and best spectacle-corrected visual acuities, sphere and cylinder refraction, topography, tomography, aberrometry, and endothelial cell count evaluated at baseline and follow-up at 1, 3, 6, 12, and 24 months after treatment. Topography was also recorded intraoperatively.

Results  Two years after treatment, mean baseline uncorrected and best spectacle-corrected visual acuities improved significantly (P = .048 and <.001, respectively) and mean spherical equivalent refraction decreased significantly (P = .03). Mean baseline flattest and steepest meridians on simulated keratometry, simulated keratometry average, mean average pupillary power, and apical keratometry all decreased significantly (P < .03). Deterioration of the Klyce indices was observed in the untreated contralateral eyes but not in treated eyes. Total corneal wavefront aberrations Z₀ (piston), Z₂ (defocus), and Z₇ (III coma) decreased significantly (P ≤ .046). Mean 12-month baseline pupil center pachymetry and total corneal volume decreased significantly (P = .045). Endothelial cell counts did not change significantly (P = .13).

Conclusions  Two years postoperatively, corneal collagen cross-linking appears to be effective in improving uncorrected and best spectacle-corrected visual acuities in eyes with progressive keratoconus by significantly reducing corneal average pupillary power, apical keratometry, and total corneal wavefront aberrations.

Methods  In this cross-sectional observational study, subjects older than 40 years with PACG who had a patent laser peripheral iridotomy underwent UBM in 1 eye. Ultrasound biomicroscopy images were qualitatively analyzed using standardized criteria. Plateau iris in a quadrant was defined by anteriorly directed ciliary body, absent ciliary sulcus, steep iris root from its point of insertion followed by a downward angulation, flat iris plane, and irido-angle contact. At least 2 quadrants had to fulfill these UBM criteria for an eye to be classified as having plateau iris.

Results  One hundred eleven subjects (70 from Singapore, 41 from Thailand) with PACG were recruited. The mean (SD) age was 65.6 (8.1) years, and 63.9% were female. Based on standardized UBM criteria, plateau iris was found in 36 of 111 eyes (32.4%; 95% confidence interval, 24.4%-41.6%). In these 36 eyes, quadrant-wise analysis showed 66.7% had plateau iris in 2 quadrants; 22.2%, in 3 quadrants; and 11.1%, in all quadrants.

Conclusions  About 30% of PACG eyes with a patent laser peripheral iridotomy were found to have plateau iris on UBM, highlighting the importance of non–pupil block mechanisms in Asian individuals.

Methods  In 93 patients with unilateral normal-tension glaucoma, intereye comparison of baseline spherical equivalent, central corneal thickness, untreated intraocular pressure, disc area, and zone β variables was performed among the following 4 subgroups classified according to age and visual field pattern standard deviation of the eye with glaucoma: subgroup 1 (age ≤50 years and visual field pattern standard deviation ≤8 dB), subgroup 2 (≤50 years and >8 dB), subgroup 3 (>50 years and ≤8 dB), and subgroup 4 (>50 years and >8 dB).

Results  Fourteen, 27, 30, and 22 patients were included in subgroups 1, 2, 3, and 4, respectively. The untreated intraocular pressure in subgroup 1 (P = .005), the zone β variables in subgroup 2 (P < .001), and both the untreated intraocular pressure (P = .010 and P = .034, respectively) and the zone β variables (P ≤ .008 and P ≤ .006, respectively) in subgroups 3 and 4 were significantly greater in the eyes with glaucoma than in the normal contralateral eyes (by paired t test or Wilcoxon signed rank test). The other variables showed no significant difference between the eyes in any subgroup.

Conclusion  The zone β variables (and not the untreated intraocular pressure) may represent significant risk factors in young patients having normal-tension glaucoma with moderate to severe visual field loss.

Methods  Case notes of 50 consecutive patients with cataract surgery performed using the SLIMCE technique were retrospectively reviewed. Clinical outcomes 3 months after surgery were analyzed, including postoperative uncorrected visual acuity, best-corrected visual acuity, intraoperative and postoperative complications, endothelial cell loss, and surgically induced astigmatism using the vector analysis method.

Results  At the 3-month follow-up, all 50 patients had postoperative best-corrected visual acuity of at least 20/60, and 37 patients (74%) had visual acuity of at least 20/30. Uncorrected visual acuity was at least 20/68 in 28 patients (56%) and was between 20/80 and 20/200 in 22 patients (44%). No significant intraoperative complications were encountered, and sutureless wounds were achieved in all but 2 patients. At the 3-month follow-up, endothelial cell loss was 3.9%, and the mean surgically induced astigmatism was 0.69 diopter.

Conclusions  SLIMCE is a safe and effective manual cataract extraction technique with low rates of surgically induced astigmatism and endothelial cell loss. In view of its low cost, SLIMCE may have a potential role in reducing cataract blindness in developing countries.

Methods  Fifty-six pseudophakic eyes with intact capsulorrhexis were included in the study. Straylight was measured with a straylight meter before and after pupil dilation. Capsulorrhexis and pupil diameter were measured and opacity of the anterior capsule was graded (on a scale of 0-5) with the slitlamp. Capsulorrhexis size and opacity were compared with the difference in straylight values between natural and dilated pupils.

Results  The mean capsulorrhexis diameter was 4.5 mm (range, 2.9-6.2 mm). Most anterior capsular rims were opaque in the area of contact with the intraocular lens (62.5% higher than grade 1). Mean straylight before pupil dilation was log_s=1.25 (range, 0.68-2.13), which increased to 1.46 (range, 0.88-2.22) after pupil dilation, which corresponds to a 62% increase (P <.001). The effect of capsulorrhexis size and opacity on the increase in straylight in scotopic conditions can be quantified by the following formula: s = 19 x (grading of anterior capsular rim) x (fraction of pupil area covered by rhexis).

Conclusions  The influence of size and opacity of the capsulorrhexis via straylight is described in a quantitative model. Capsulorrhexis size must be greater than 4 mm to prevent functional problems at night.

Methods  Prospective clinical study of 61 of 800 consecutive eyes (7.6%) (61 of 782 patients) seen at a university hospital during the 48-month study for primary rhegmatogenous retinal detachment in whom no break could be identified preoperatively despite thorough examinations. All of the patients underwent pars plana vitrectomy alone with meticulous peripheral vitreous dissection assisted by diffuse illumination, a wide-angle viewing system, perfluorocarbon liquid, triamcinolone acetonide suspension, and balanced salt solution to identify and manage primary retinal breaks.

Results  Retinal breaks were found intraoperatively in 60 eyes (98%). In 51 of 61 eyes (84%), balanced salt solution was left in the vitreous cavity. Best-corrected visual acuity was 20/40 or better in 25 of 61 study eyes (41%). Primary retinal reattachment was attained in 60 study eyes (98%). Final reattachment was achieved in all 61 eyes (100%).

Conclusions  Pars plana vitrectomy alone with diffuse illumination and extensive vitreous dissection led to identification and management of retinal breaks undetectable before surgery, achieving a high primary reattachment rate.

Methods  In 5 patients (5 eyes) with characteristic MEWDS lesions (hypofluorescent in the late phase of indocyanine green angiography [IA]), results of microperimetric retinal sensitivity examination and IA were compared with findings from enhanced spectral-domain optical coherence tomography (SD-OCT) at diagnosis and until clinical resolution.

Results  Enhanced SD-OCT revealed moderately reflective focal lesions within the outer photoreceptor layer, where the inner and outer segment junction was disrupted, that corresponded with hypofluorescent areas in the late phase of IA. Areas of decreased retinal sensitivity on microperimetric examination matched areas of disruption in the inner/outer segment junction on SD-OCT images. In the first month after diagnosis, microperimetric examination and enhanced SD-OCT showed a shift in areas of decreased retinal sensitivity and disruption in the inner/outer segment junction from around the optic disc to the temporal macula. Retinal sensitivity and the inner/outer segment junction returned to almost normal in all eyes about a month after diagnosis of MEWDS.

Conclusion  Enhanced SD-OCT revealed abnormalities in the photoreceptor layer that were specific to MEWDS and that, with retinal shape and function, seemed to change location during clinical recovery from MEWDS.

Methods  A national, prospective, population-based study was performed in Sweden from April 1, 2004, to March 31, 2007. The ophthalmologic part of the study was separately organized, and screening for ROP was performed beginning postnatal week 5. The criteria for the treatment of ROP agreed with the recommendations of the Early Treatment for Retinopathy of Prematurity Cooperative Group.

Results  During the study, 506 of 707 live-born infants survived until the first eye examination. Of these, 368 (72.7%) had ROP: 37.9% had mild ROP and 34.8% had severe ROP. Ninety-nine infants (19.6%) were treated. Gestational age at birth was a stronger predictor of ROP than was birth weight. A log-linear relationship between severe ROP and gestational age at birth was found in the present cohort, and the risk of ROP was reduced by 50% for each week of increase in gestational age at birth.

Conclusions  Today, extremely preterm infants are surviving, and this population-based study with ROP as a primary outcome shows a higher incidence of this condition than in previously reported national cohorts.

Methods  Descemet stripping automated endothelial keratoplasty grafts were produced by seeding cultured HCEC suspensions onto human corneal stromal discs. Three insertion techniques were assessed in an ex vivo model. The feasibility of DSAEK grafts with cultured HCECs was examined in a rabbit model. Rabbits received stromal disc transplants with cultured HCECs (c-DSAEK) or without HCECs (controls).

Results  The HCECs on the DSAEK grafts had a consistent size and polygonal shape. Mean (SD) percentage of cell loss in the taco-folding group (38.7% [5.2%]) was significantly greater than that in the Busin glide (11.6% [1.5%]; P = .001) and lens glide (18.0% [5.4%]; P = .007) groups. Corneal transparency gradually recovered in the c-DSAEK group, whereas edema persisted for up to 28 days in controls. Histologic examination after surgery revealed donor HCECs covering the posterior surface of the graft in the c-DSAEK group.

Conclusions  Further enhancements of the efficacy and safety of DSAEK using cultured HCECs will make this a clinically feasible alternative therapy for corneal endothelial dysfunction.

Clinical Relevance  Descemet stripping automated endothelial keratoplasty using cultured HCECs may be a novel therapeutic approach to treat corneal endothelial dysfunction.

Methods  JSM6427 selectivity for 5β1 was evaluated by in vitro binding assays while the ability of JSM6427 to inhibit CNV was investigated in a laser-induced monkey model and a growth factor–induced rabbit model. Intravitreal injections of JSM6427 (100, 300, or 1000 µg) or vehicle were administered immediately after the CNV induction procedure and at weekly intervals for 4 weeks. Fluorescein angiography was performed weekly. Ocular tolerability was evaluated ophthalmoscopically and histologically in both models; additional assessments in monkeys included electroretinography, biomicroscopy, pathological examination, and analysis of JSM6427 pharmacokinetics.

Results  JSM6427 was highly selective for the 5β1-fibronectin interaction. Weekly intravitreal injections of JSM6427 resulted in a statistically significant dose-dependent inhibition of CNV in laser-induced and growth factor–induced models without any ocular JSM6427-related adverse effects. JSM6427 was cleared through the systemic circulation with no evidence of systemic accumulation.

Conclusions  Intravitreal JSM6427 provided dose-dependent inhibition of CNV in monkey and rabbit experimental models.

Clinical Relevance  JSM6427 may provide a new approach for the treatment of ocular neovascular diseases such as age-related macular degeneration in humans.

Methods  The Blue Mountains Eye Study (BMES) followed up 3654 participants 49 years and older (BMES 1, 1992-1994), including 2335 (75.3% of survivors) at the 5-year (BMES 2, 1997-1999) and 1952 (76.5%) at the 10-year (BMES 3, 2002-2004) examinations. Age-related macular degeneration retinal photographic grading used the Wisconsin system. Early and late AMD included prevalent and incident cases from all visits. CFH genotyping used TaqMan assays.

Results  Of 767 AMD cases, 53.3% of early and 53.1% of late AMD cases were bilateral. After adjusting for age and other covariants, the CFH CC (Y402H polymorphism) genotype was associated with an increased likelihood of bilateral compared with unilateral involvement by any soft drusen (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.4-4.5), distinct soft drusen (OR, 2.8; 95% CI, 1.0-8.1), and pigmentary abnormalities (OR, 1.7; 95% CI, 1.0-2.8). We could not establish significant associations between this genotype and the bilaterality of late AMD (OR, 1.8; 95% CI, 0.4-7.7), either geographic atrophy (OR, 0.6; 95% CI, 0.07-4.6) or neovascular AMD (OR, 3.4; 95% CI, 0.3-41.4).

Conclusions  Persons with the CFH CC genotype at any given age have an increased likelihood of bilateral compared with unilateral involvement of some early AMD lesions.

Methods  The Blue Mountains Eye Study examined 3654 persons 49 years and older (82.4% response) during 1992-1994 and after 5 and 10 years. Australian National Death Index data confirmed deaths until 2005. Visual impairment was defined as presenting, correctable, and noncorrectable, using better-eye visual acuity. Associations between visual impairment and mortality risk were estimated using Cox regression and structural equation modeling.

Results  After 13 years, 1273 participants had died. Adjusting for mortality risk markers, higher mortality was associated with noncorrectable visual impairment (hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.04-1.75). This association was stronger for ages younger than 75 years (HR, 2.58; 95% CI, 1.42-4.69). Structural equation modeling revealed greater effects of noncorrectable visual impairment on mortality risk (HR, 5.25; 95% CI, 1.97-14.01 for baseline ages <75 years), with both direct (HR, 2.16; 95% CI, 1.11-4.23) and indirect (HR, 2.43; 95% CI, 1.17-5.03) effects. Of mortality risk markers examined, only disability in walking demonstrated a significant indirect pathway for the link between visual impairment and mortality.

Conclusions  Visual impairment predicted mortality by both direct and indirect pathways, particularly for persons younger than 75 years with noncorrectable visual impairment. Disability in walking, which can substantially influence general health, represented a major indirect pathway.

Methods  A population-based study was conducted in 3280 (78.7% response) Malay adults aged 40 to 80 years. Diabetes was defined as a random serum glucose level of 200 mg/dL or greater or physician diagnosis of diabetes mellitus. Metabolic abnormalities including body mass index, lipid levels, and blood pressure were measured. Glaucoma was defined from a standardized examination by means of the International Society for Geographical and Epidemiological Ophthalmology criteria.

Results  There were 764 persons (23.3%) who had diabetes. After controlling for age, sex, education, smoking, central corneal thickness, and diabetes treatment, intraocular pressure was higher in persons with than without diabetes (16.7 vs 15.0 mm Hg, P < .001) and in those with higher serum glucose levels (P < .001), glycosylated hemoglobin concentrations (P < .001), total cholesterol levels (P = .001), triglyceride levels (P = .002), and body mass index (P = .001). However, the prevalence of glaucoma was similar between persons with and without diabetes (4.7% vs 4.5%). In multivariate logistic regression models adjusting for age, sex, education, smoking, central corneal thickness, and diabetes treatment, diabetes was not associated with glaucoma (odds ratio, 1.00; 95% confidence interval, 0.63-1.61).

Conclusion  These data suggest that, although diabetes and metabolic abnormalities may be associated with a small increase in intraocular pressure, they are not significant risk factors for glaucomatous optic neuropathy.

Methods  Random cluster sampling was used to identify the adults 50 years and older living in the Liwan district of Guangzhou, China. Presenting visual acuity (PVA) with habitual correction and best-corrected visual acuity (BCVA) based on autorefraction and subjective refraction were measured using the Early Treatment Diabetic Retinopathy Study visual chart. Blindness and low vision were defined according to World Health Organization criteria. Eyes with visual impairment were assigned 1 principal cause for the impairment.

Results  Visual acuity measurements were available for 1399 adults 50 years and older (75.3% participation rate). The prevalence of blindness and low vision based on the PVA was 0.6% (95% confidence interval, 0.2%-1.0%) and 10.1% (95% confidence interval, 8.5%-11.7%), respectively. These rates were reduced to 0.5% and 3.1% when the BCVA was considered. Based on the PVA, the principal causes for blindness were cataract (39.6%), glaucoma (11.0%), and myopic maculopathy (6.6%). The majority of low vision cases were attributable to cataract (45.3%) and uncorrected refractive error (43.9%).

Conclusion  The majority of eye diseases leading to visual impairment are potentially treatable in this population.

Methods  A total of 286 control subjects (126 men and 160 women) and 159 white patients (73 men and 86 women) harboring exudative AMD in 1 eye were recruited. A third group of 182 DNA samples from blood donors of the same geographical areas were also typed to assess the frequency of CFH Tyr402His and ARMS2 del443ins54 polymorphisms in the general population. The data were analyzed statistically by a standard 2 x 2 table, Fisher exact tests, and odds ratios.

Results  The deletion-insertion at chromosome 10q26 (del443ins54) showed the strongest association with AMD in terms of both P value and odds ratio (P = 2.7 x 10^–15; odds ratio = 3.25), and a highly significant association was also confirmed for Tyr402His at the CFH locus (P = 9.9 x 10^–13; odds ratio = 2.86). We found no differences in allele and genotype association between classic and occult choroidal neovascularization. We also observed that 39% of the samples in the general Italian population were at least 5.4 times more likely than control subjects to develop AMD.

Conclusions  To our knowledge, this is the first confirmation of the association of del443ins54 in Italian patients with AMD, and we also confirmed the association of Tyr402His with CFH. Genetic analysis of the general population suggested that analysis of the ARMS2 and CFH risk alleles alone may be helpful in differentiating high-risk individuals (odds ratio > 5.00) from low-risk individuals (odds ratio < 0.45).

Clinical Relevance  Individuals at high risk for developing AMD could be identified and selected for specific prevention programs. In this context, the development of prevention programs based on dietary antioxidants or on close monitoring of at-risk individuals should be considered or suggested.

Methods  Peripheral blood was collected in EDTA for genomic DNA isolation from leukocytes of all affected and unaffected individuals. Amplification of transforming growth factor β-induced gene (TGFBI) using polymerase chain reaction followed by direct sequencing was carried out to determine the mutations underlying the disorder. A detailed clinical evaluation was undertaken to establish a genotype-phenotype correlation.

Results  R124H mutation resulting from a missense heterozygous substitution of G to A at nucleotide 418 of TGFBI was detected in all affected members of the 2 families. The affected individuals were clinically diagnosed as having granular corneal dystrophy. Histopathological examination was not done because no surgical intervention was undertaken.

Conclusions  To our knowledge, this is the first report of Avellino corneal dystrophy from India clinically diagnosed as granular corneal dystrophy, emphasizing that TGFBI screening is essential for the accurate diagnosis and classification of corneal dystrophies.

Clinical Relevance  Molecular genetics is a useful tool for accurate diagnosis and classification of corneal dystrophies. All autosomal dominant stromal dystrophies should be screened for underlying mutations in TGFBI because the clinical and phenotypic appearance is variable.

Methods  Adults with impaired vision, visual acuity worse than 20/40, were recruited from clinics, vision rehabilitation agencies, and support groups. Participants completed daily diaries for 12 months, entering information on the amount of time they used caregivers and providers and types of care. Demographic information was obtained from questionnaires. The cost of care was calculated using mean hourly wage rates.

Results  The mean age of the 114 participants was 66.5 years (standard deviation [SD], 19.7) with 64% of participants female; 105 of 114 participants relied on a caregiver at least once during the 12 months. The mean amount of yearly caregiver time used was 152.2 hours (SD, 193; median, 81.3; range, 1-851 hours). The median time represents 4.6% of a working week. There were no significant associations of age, sex, type, or place of residence with the amount of care received (P ≥ .1). As most of the caregivers were family members who assisted with transport, written communications, and personal affairs, the "opportunity costs" were calculated. The median annual opportunity cost was A$915 (US $710) (range, $A0-$9653 [US $0-$7491]).

Conclusions  This study prospectively obtained data for the cost of caregivers for people with impaired vision. The degree of vision impairment was not associated with the amount of care used but showed a threshold effect: when vision is impaired to the extent that people cannot legally hold a driver's license, reliance on caregivers appears to be independent of the severity of loss of vision.

Methods  Multicenter, randomized, clinical trial of 271 participants.

Main Outcome Measure  Gain in visual acuity letter score of 15 or more from baseline to month 12.

Results  Seven percent, 27%, and 26% of participants achieved the primary outcome in the observation, 1-mg, and 4-mg groups, respectively. The odds of achieving the primary outcome were 5.0 times greater in the 1-mg group than the observation group (odds ratio [OR], 5.0; 95% confidence interval [CI], 1.8-14.1; P = .001) and 5.0 times greater in 4-mg group than the observation group (OR, 5.0; 95% CI, 1.8-14.4; P = .001); there was no difference identified between the 1-mg and 4-mg groups (OR, 1.0; 95% CI, 0.5-2.1; P = .97). The rates of elevated intraocular pressure and cataract were similar for the observation and 1-mg groups, but higher in the 4-mg group.

Conclusions  Intravitreal triamcinolone is superior to observation for treating vision loss associated with macular edema secondary to CRVO in patients who have characteristics similar to those in the SCORE-CRVO trial. The 1-mg dose has a safety profile superior to that of the 4-mg dose.

Application to Clinical Practice  Intravitreal triamcinolone in a 1-mg dose, following the retreatment criteria applied in the SCORE Study, should be considered for up to 1 year, and possibly 2 years, for patients with characteristics similar to those in the SCORE-CRVO trial.

Trial Registration  clinicaltrials.gov Identifier: NCT00105027

Methods  Multicenter, randomized clinical trial of 411 participants.

Main Outcome Measure  Gain in visual acuity letter score of 15 or more from baseline to month 12.

Results  Twenty-nine percent, 26%, and 27% of participants achieved the primary outcome in the standard care, 1-mg, and 4-mg groups, respectively. None of the pairwise comparisons between the 3 groups was statistically significant at month 12. The rates of elevated intraocular pressure and cataract were similar for the standard care and 1-mg groups, but higher in the 4-mg group.

Conclusions  There was no difference identified in visual acuity at 12 months for the standard care group compared with the triamcinolone groups; however, rates of adverse events (particularly elevated intraocular pressure and cataract) were highest in the 4-mg group.

Application to Clinical Practice  Grid photocoagulation as applied in the SCORE Study remains the standard care for patients with vision loss associated with macular edema secondary to BRVO who have characteristics similar to participants in the SCORE-BRVO trial. Grid photocoagulation should remain the benchmark against which other treatments are compared in clinical trials for eyes with vision loss associated with macular edema secondary to BRVO.

Trial Registration  clinicaltrials.gov Identifier: NCT00105027

Methods  We reviewed the medical records of 43 660 consecutive patients. Eyes with glaucomatous optic neuropathy, 10 or more Swedish Interactive Threshold Algorithm standard 24-2 visual fields in at least 5 years, and mean deviation (MD) smaller than –6.0 dB were included. Pointwise linear regression was used to determine progression. Cox proportional hazards analysis was used to calculate risk of progression based on different baseline covariates.

Results  We enrolled 205 eyes (205 patients; mean [SD] age, 64.2 [11.0] years; follow-up, 6.5 [1.8] years; number of visual fields, 12.3 [2.9]). Patients were divided into 3 groups: initial superior defect (group A; n = 79; MD, –3.4 [1.9] dB), initial inferior defect (group B; n = 61; MD, –3.4 [1.8] dB), and both hemifields affected (group C; n = 65; MD, –4.2 [1.5] dB). Group C progressed faster than did groups A and B (P < .02). Multivariate analysis showed significant effect of higher baseline intraocular pressure, thinner central corneal thickness, and initial damage to both hemifields.

Conclusions  Initial damage to both hemifields increases the risk of glaucoma progression. More aggressive therapy should be considered for these eyes.

Design  A prospective, multicenter observational cohort study of 1221 participants of African descent and European descent with no glaucoma (normal), suspected glaucoma, and glaucoma. Six hundred eighty-six patient participants in the African Descent and Glaucoma Evaluation Study will be followed up longitudinally. Four hundred thirty-six participants of European descent from the Diagnostic Innovations in Glaucoma Study (DIGS) were also included. Baseline demographics, visual function (standard automated perimetry, short-wavelength automated perimetry, frequency doubling technology perimetry), optic nerve structure (retina tomography, optical coherence tomography), clinical status, and risk factors were measured.

Results  Individuals of African descent had (1) thinner corneas (P < .001) across all diagnostic groups, (2) a higher percentage of reported diabetes mellitus (P < .001) and high blood pressure (P < .001) and a lower percentage of reported heart disease (P = .001), and (3) worse pattern standard deviation for standard automated perimetry fields overall (P = .001) and within normal limits (P = .01) than individuals of European descent. No differences were present for mean intraocular pressure (P = .79).

Conclusions  Significant baseline differences were found in a number of clinical findings between persons of African descent compared with European descent. Longitudinal data from the African Descent and Glaucoma Evaluation Study will be important for determining which baseline features are important and predictive for accurate diagnosis and follow-up in this high-risk group.

Trial Registration  clinicaltrials.gov Identifier: NCT00221923.

Methods  Eligibility criteria for CAPT required 10 or more large (≥125 µm) drusen in each eye. Readers graded baseline photographs from all participants and all follow-up photographs from 402 untreated eyes. Drusen and pigment characteristics were used to assign the AREDS scale score. Choroidal neovascularization was identified from fluorescein angiograms. Geographic atrophy involving the macular center was identified from color photographs.

Results  Among 1001 untreated eyes, 90% were at steps 5 to 7 at baseline. The 5-year incidence of advanced age-related macular degeneration (AMD) increased with each step from 8% (step 4) to 40% (steps 8 and 9 combined). These rates were similar to those reported in AREDS. Among 261 eyes with all 5 annual photograph gradings available and without progression to advanced AMD, 55% of eyes had scores that indicated improvement at least once. Before progression to advanced AMD, only 32% of 141 eyes either went through step 8 or 9 or had an increase of 2 or more steps from baseline.

Conclusions  The AREDS 9-step severity scale was predictive of development of advanced AMD. The AREDS scale has deficiencies as a surrogate outcome for progression to advanced AMD.

Methods  The International Thyroid Eye Disease Society conducted a structured, 3-round Delphi exercise establishing consensus for a core set of measures for clinical trials in thyroid eye disease. The steering committee discussed the results in a face-to-face meeting (nominal group technique) and evaluated each criterion with respect to its feasibility, reliability, redundancy, and validity. Redundant measures were consolidated or excluded.

Results  Criteria were parsed into 11 domains for the Delphi surveys. Eighty-four respondents participated in the Delphi 1 survey, providing 220 unique items. Ninety-two members (100% of the respondents from Delphi 1 plus 8 new participants) responded in Delphi 2 and rated the same 220 items. Sixty-four members (76% of participants) rated 153 criteria in Delphi 3 (67 criteria were excluded because of redundancy). Criteria with a mean greater than 6 (1 = least appropriate to 9 = most appropriate) were further evaluated by the nominal group technique and provisional core measures were chosen.

Conclusions  Using a Delphi exercise, we developed provisional core measures for assessing disease activity and severity in clinical trials of therapies for thyroid eye disease. These measures will be iteratively refined for use in multicenter clinical trials.

Methods  Hartley strain guinea pigs were infected via an aerosol route with virulent Mycobacterium tuberculosis. One group of guinea pigs was infected with a relatively low bacterial inoculum and received no treatment. A second group of guinea pigs received high-dose infection and were treated with the first-line anti-TB drugs isoniazid, rifampin, and pyrazinamide. Development of ocular TB lesions was documented by histological analysis, acid-fast staining, and real-time polymerase chain reaction for M tuberculosis DNA.

Results  Untreated guinea pigs developed pulmonary and extrapulmonary TB. Ocular TB, primarily involving the uvea, developed in 5 of 12 eyes (42%). Uveal granulomatous lesions showed the presence of acid-fast organisms and M tuberculosis DNA. In treated animals, none of the 8 eyes examined revealed the presence of acid-fast organisms; however, there was mild nongranulomatous uveitis in 4 eyes.

Conclusions  Mycobacterium tuberculosis delivered via aerosol to guinea pigs results in extrapulmonary dissemination to the eye. Of significance, intraocular changes in this model include granulomatous inflammation and the presence of acid-fast organisms, as seen in human cases of ocular TB.

Clinical Relevance  The guinea pig model may provide greater insight into the pathogenesis of intraocular TB and assist in the development of novel modalities to treat this global infectious disease.

Methods  Fundus photographs from 181 of 4757 AREDS participants with a GA area of at least 0.5 disc areas at baseline or from participants who developed bilateral GA during follow-up were scanned, digitized, and evaluated longitudinally. Geographic atrophy area was determined using planimetry. Rates of progression from noncentral to central GA and of vision loss following development of central GA included the entire AREDS cohort.

Results  Median initial lesion size was 4.3 mm². Average change in digital area of GA from baseline was 2.03 mm² (standard error of the mean, 0.24 mm²) at 1 year, 3.78 mm² (0.24 mm²) at 2 years, 5.93 mm² (0.34 mm²) at 3 years, and 1.78 mm² (0.086 mm²) per year overall. Median time to developing central GA after any GA diagnosis was 2.5 years (95% confidence interval, 2.0-3.0). Average visual acuity decreased by 3.7 letters at first documentation of central GA, and by 22 letters at year 5.

Conclusions  Growth of GA area can be reliably measured using standard fundus photographs that are digitized and subsequently graded at a reading center. Development of GA is associated with subsequent further growth of GA, development of central GA, and loss in central vision.

Methods  Longitudinal population-based study of persons with type 1 diabetes mellitus who received care for their diabetes in south central Wisconsin from July 1, 1979, to June 30, 1980. Data for this investigation were obtained from the 1990-1992 through the 2005-2007 follow-up examinations. Main outcome measures included the severity of diabetic retinopathy (DR) and macular edema (ME).

Results  In the 1990-1992 prevalence data, soluble vascular cell adhesion molecule, tumor necrosis factor, and homocysteine levels were associated with increased odds of more severe DR (odds ratios [highest vs lowest quartile], 3.95 [95% confidence interval, 1.66-9.39], 5.46 [2.38-12.52], and 7.46 [2.91-19.16], respectively) in those with kidney disease while controlling for relevant confounders. Similar odds were found for proliferative DR. Only total homocysteine level was associated with increased odds of ME (3.80 [95% confidence interval, 1.91-7.54]), irrespective of kidney disease. None of the markers were associated with incidence of proliferative DR, ME, or progression of DR 15 years later.

Conclusions  A limited number of markers are associated with increased odds of prevalent retinal outcomes in persons with type 1 diabetes mellitus and kidney disease. Only homocysteine level is associated with ME in those with and without kidney disease. In the absence of kidney disease, the markers do not add to the more conventional descriptors and predictors of DR in persons with type 1 diabetes mellitus. This may reflect the close association of DR and kidney disease in diabetic persons.

Data Sources  Some cost data were taken from a previous search conducted for 1995 to 2006 and we searched MEDLINE and Scopus and Google for more recent data (2006 and 2007).

Study Selection  Articles were identified from the literature using "cataract surgery" in combination with the terms outcome or visual acuity. Additional searches were conducted using individual countries as a term in combination with VA, outcome, or cost. Regression curves were constructed from utility values derived from a TTO study and VA data. Gains in quality-adjusted life-years (QALYs) were calculated based on life expectancy tables from the World Health Organization and discounts of 3% for both cost and benefit. Sensitivity analyses explored the effect of changes in discounting, life expectancy, preoperative VA, and cost.

Data Extraction  If the data were usable, they were kept; otherwise they were discarded.

Data Synthesis  Preoperative VA (logMAR) correlated with increasing gross national income per capita (Pearson correlation coefficient, –0.784; P < .001) and showed that in developing countries preoperative vision is much poorer compared with developed countries. Cost utility data ranged from $3.5 to $834/QALY in developing countries to $159 to $1356/QALY in developed countries. Sensitivity analysis showed that changing life expectancy, VA, and discount rate resulted in moderate changes.

Conclusions  The TTO approach demonstrates that cataract surgery is extremely cost-effective.

Methods  Ninety students were randomly divided into 3 classes (30 students per class). The first class studied under a didactic model. The other 2 classes were divided into 6 groups (10 students per group) and received PBL teaching; 3 groups studied via cases presented in digital form and the others studied via paper-form cases. The results of theoretical and case analysis examinations were analyzed using the ² test. Student performance on the interval practice was analyzed using the Kruskal-Wallis test. Questionnaires were used to evaluate student and facilitator perceptions.

Results  Students in the digital groups exhibited better performance in the practice procedures according to tutorial evaluations compared with the other groups (P < .05). The 2 PBL classes had significantly higher mean results of theoretical and case analysis examinations (P < .001), but there was no significant difference between the 2 PBL classes. Ninety-three percent of students in the digital groups (vs 73% in the paper groups) noted that the cases greatly stimulated their interest.

Conclusions  Introducing PBL into ophthalmology could improve educational quality and effectiveness. Digital PBL cases stimulate interest and motivate students to further improve diagnosis and problem-handling skills.

Methods  Retrospective medical record and pathologic specimen review of 20 patients treated for sebaceous carcinoma at a tertiary care center. Biopsies with artifactual loss of or damage to the epithelium were categorized as nondiagnostic.

Results  One hundred forty-four map biopsies were reviewed, an average of 7.2 (standard deviation [SD], 4.4) biopsies per patient. Sixteen patients had extensive pagetoid tumor, 4 did not. Fifteen percent of biopsies were nondiagnostic. The frequency of nondiagnostic biopsies in patients with and without extensive pagetoid tumor was 37% and 10%, respectively. The odds ratio of nondiagnostic biopsy in the setting of extensive pagetoid tumor was 5.9 (95% confidence interval, 2.3-15.6; P = .004). Six of the sixteen patients (38%) without extensive pagetoid tumor had at least 1 nondiagnostic biopsy, with an average of 1.8 (SD, 1.6) nondiagnostic biopsies per patient (22% of biopsies). Two of the 4 patients (50%) with extensive pagetoid tumor had at least 1 nondiagnostic biopsy, with an average of 5.5 (SD, 3.5) nondiagnostic biopsies per patient (57% of biopsies).

Conclusions  Nondiagnostic, de-epithelialized conjunctival map biopsies are more common in patients with extensive pagetoid tumor than in those with limited or no pagetoid tumor. Artifactual epithelial loss may result from disruption of epithelial adhesion to the basement membrane by infiltrating tumor cells.

Methods  Protein expression and localization of WT1 and Bcl2 were studied by means of immunolabeling and semiquantification in 123 conjunctival melanocytic lesions (71 benign nevi, 21 atypical nevi, 11 primary acquired melanosis, and 20 malignant melanomas). Ancillary immunohistochemical studies were performed with Bcl2, S100, HMB45, and Melan A antibodies.

Results  WT1 showed a graded increase in expression in lesions with increasing atypia. Higher mean numbers of WT1-positive cells correlated with increasing atypia in melanocytes. In all cases, Bcl2 expression was positive and more robust than was S100, HMB45, or Melan A expression. WT1 and HMB45 frequently showed diffuse and strong staining in atypical nevi, primary acquired melanosis with atypia, and malignant melanomas compared with benign lesions.

Conclusions  Bcl2 is a highly sensitive immunohistochemical marker for melanocytic tumors of the conjunctiva; HMB45 and WT1 staining distinguishes benign from malignant lesions.

Clinical Relevance  Our results show that HMB45 and WT1 immunolabeling is helpful in the evaluation of conjunctival melanocytic lesions. Accordingly, we recommend the development of an immunohistochemical panel to classify these lesions.

Methods  This was a retrospective clinicoimmunopathologic study. Routine histochemical staining was performed with multiparametric immunohistochemical analysis with monoclonal antibodies immunoreacted on paraffin sections to identify the following cell antigens: S-100, MART-1, HMB-45, CD45, CD68, CD1a, lysozyme, and Ki-67 (nuclear proliferation protein).

Results  A unique granular cell nevus contained periodic acid–Schiff–positive, diastase-resistant granules and immunoreacted with monoclonal antibodies against S-100 protein and melanocytic-associated antigens MART-1 and HMB-45. Results for CD45, CD1a, CD68, and lysozyme immunostaining of the granular cells were negative. Two epithelioid cell (clonal or inverted) nevi exhibited an identical immunohistochemical profile. Only the balloon cell nevus was MART-1–positive and HMB-45–negative. The granular cell and blue nevi immunoreacted negligibly with Ki-67 (approximately 1% of cells).

Conclusions  S100 and MART-1 reliably immunostained all nevocytic morphologic variants. HMB-45 immunoreactivity of the granular, epithelioid/clonal, and blue nevi did not indicate a more active or proliferative lesion but instead suggested abnormal melanogenesis. Ki-67 was the most valuable immunohistochemical adjunct to morphology for the diagnosis of these benign variant conjunctival nevi, because melanomas display a much higher proliferation index (>10% nuclear positivity among all cells counted) than the current nevi (approximately 1%).

Methods  This was a retrospective medical record review of 2514 consecutive eyes; Kaplan-Meier estimates and Cox regression analyses were used.

Results  The median tumor basal diameter was 5.0 mm and thickness was 1.5 mm. Nevus growth into melanoma occurred in 2%, 9%, and 13% of eyes at 1, 5, and 10 years, respectively. Factors predictive of growth into melanoma by multivariable analysis included tumor thickness greater than 2 mm (P < .001), subretinal fluid (P = .002), symptoms (P = .002), orange pigment (P < .001), tumor margin within 3 mm of the optic disc (P = .001), ultrasonographic hollowness (P < .001), and halo absence (P = .009). A mnemonic device to recall risk factors of ocular melanoma is "To find small ocular melanoma using helpful hints," representing thickness, fluid, symptoms, orange pigment, margin, ultrasonographic hollowness, and halo absence. The median hazard ratio for those with 1 to 2 risk factors was 3; for 3 or 4 factors, 5; for 5 to 6 factors, 9; and for all 7 factors, 21.

Conclusions  In an analysis of 2514 choroidal nevi, factors predictive of growth into melanoma included greater thickness, subretinal fluid, symptoms, orange pigment, margin near disc, and 2 new features: ultrasonographic hollowness and absence of halo.

Methods  Retrospective medical record review.

Results  The mean (median) patient age was 58 (59) years. A total of 8033 eyes were examined. Of the 285 eyes with iris melanoma, the mean tumor thickness was 2.7 mm and metastasis occurred in 0.5%, 4%, and 7% at 3, 5, and 10 years, respectively. Of the 492 eyes with ciliary body melanoma, the mean tumor thickness was 6.6 mm and metastasis occurred in 12%, 19%, and 33% at 3, 5, and 10 years, respectively. Of the 7256 eyes with choroidal melanoma, the mean tumor thickness was 5.5 mm and metastasis occurred in 8%, 15%, and 25% at 3, 5, and 10 years, respectively. For all uveal melanoma, metastasis at 5, 10, and 20 years was 6%, 12%, and 20% for small melanoma (0-3.0 mm thickness), 14%, 26%, and 37% for medium melanoma (3.1-8.0 mm), and 35%, 49%, and 67% for large melanoma (>8.0 mm). More specifically, metastasis per millimeter increment at 10 years was 6% (0-1.0 mm thickness), 12% (1.1-2.0 mm), 12% (2.1-3.0 mm), 16% (3.1-4.0 mm), 27% (4.1-5.0 mm), 28% (5.1-6.0 mm), 29% (6.1-7.0 mm), 41% (7.1-8.0 mm), 50% (8.1-9.0 mm), 44% (9.1-10.0 mm), and 51% (>10.0 mm). Clinical factors predictive of metastasis by multivariate analysis included increasing patient age, ciliary body location, increasing tumor diameter, increasing tumor thickness, having a brown tumor, and the presence of subretinal fluid, intraocular hemorrhage, or extraocular extension.

Conclusion  Increasing millimeter thickness of uveal melanoma is associated with increasing risk for metastasis.

Methods  Retrospective review of medical records.

Results  The primary tumors included skin melanoma (4 [20%]), uveal melanoma (4 [20%]), breast carcinoma and conjunctival melanoma (3 [15%] each), renal cell carcinoma (2 [10%]), and medullary thyroid carcinoma, prostate carcinoma, lung carcinoma, and salivary gland carcinoma (1 [5%] each). Eyelid metastasis was the first sign of systemic cancer in 3 patients (15%). The most common clinical finding at the initial examination was a solitary nodule in 12 patients (60%), a flat pigmented lesion and diffuse eyelid swelling in 3 patients each (15%), and multiple nodules and epiphora in 1 patient (5%) each. Ten patients (50%) had concomitant ocular site metastasis. Primary treatment included excision alone in 6 patients (30%), external beam radiotherapy in 7 (35%), systemic chemotherapy in 4 (20%), and observation in 3 (15%). The metastatic tumors regressed in 10 patients (50%), remained stable in 7 (35%), and showed progression in 3 (15%). After a mean follow-up of 16 months, 9 patients (45%) were alive and 11 (55%) had died of systemic metastatic disease.

Conclusions  Eyelid metastasis can display a variety of clinical features and should be considered in patients with known systemic cancer. These patients usually have multiple metastatic sites, ocular and nonocular. The systemic prognosis is poor.

Methods  We reviewed all pathology slides of patients with microscopic scleral invasion who were included in 3 prospective treatment protocols (1988-2007). All patients received adjuvant chemotherapy (moderately intensive chemotherapy in the first 2 protocols or a more intensive combination in the third one). Only patients with cut-end invasion received orbital radiotherapy.

Results  Thirty-two of 386 patients had enucleated eyes with intrascleral (21 cases) and transscleral (11 cases) invasion. Of these cases, 20 had tumor invading the optic nerve beyond the lamina cribrosa, with 6 of these having tumor at the surgical margin. Sixteen were treated with moderately intensive chemotherapy and 16 received a higher-intensity regimen. Five-year overall survival was 0.77. Seven patients had an extraocular relapse (central nervous system metastasis, n = 4; systemic metastasis, n = 2; and involving the orbit, n = 3, isolated in 1 and combined with central nervous system disease in 2). All patients who had a relapse died. Patients receiving the intensive regimen had a significantly better outcome (P = .007).

Conclusions  Microscopic scleral invasion might be a risk factor for extraocular relapse, and more intensive chemotherapy results in improved survival for these patients.

Methods  Retrospective series of 192 patients with 200 lesions diagnosed as BCC of the periocular region. All were excised en bloc with 1-mm margins beyond the clinically apparent tumor and examined using an enhanced FSC technique with stereoscopic microdissection of the surgical margins.

Results  Of 200 malignant BCCs, 93.0% represented primary tumors. The overall recurrence rate was 1.0%, with a mean follow-up of 4 years. In patients with primary lesions, the overall recurrence rate was 1.1%, with a mean follow-up of 3.9 years. There were no recurrences in the secondary tumor group after a mean follow-up of 4.8 years. Of the 200 lesions, 66.0% lesions required a single en bloc resection to achieve tumor-free margins.

Conclusions  An enhanced FSC technique using stereoscopic microdissection of the surgical margins permits greater conservation of healthy tissue and yields cure rates comparable to those of the standard FSC technique and Mohs micrographic surgery. We believe that this enhanced FSC technique is a highly effective method for resection of periocular BCC.

Methods  A retrospective multicenter cohort study of 118 cases of epithelial neoplasia was undertaken. Main outcome measures included pathologic analysis, subtyping, and survival.

Results  Of 118 cases, 17 (14%) were reclassified using the proposed expanded classification scheme based on the current World Health Organization classification of salivary gland tumors. The most frequent neoplasms were pleomorphic adenoma and adenoid cystic carcinoma, of which we highlight more unusual histologic features. Three tumors were found to be unclassifiable with the updated scheme, with 2 having histologically malignant features. Deficiencies and variations in pathologic assessment were noted. Variation in the histologic findings of pleomorphic adenoma and assessment of the extent of invasion of carcinoma ex pleomorphic adenoma were highlighted.

Conclusions  The use of the more histologically diverse classification of salivary gland tumors can be successfully applied to the epithelial lacrimal gland neoplasms. This expanded classification system led to reclassifying 14% of cases. Currently, there are no consistent pathologic standards for processing and evaluating these lesions.

Methods  Nine corneal buttons were obtained during penetrating keratoplasty from patients with keratoglobus. Histologic features were examined using hematoxylin-eosin–stained sections. Immunohistochemical staining for 1-proteinase inhibitor, Sp1, and matrix metalloproteinases 1, 2, and 3 was performed, with 2 normal and 2 corneal sections with keratoconus as controls.

Results  Hematoxylin-eosin staining revealed diffuse stromal thinning and focal disruptions in Bowman's layer in all keratoglobus specimens. Similar abnormal immunostaining results for 1-proteinase inhibitor and Sp1 were detected in keratoglobus and keratoconus at their respective active disease sites. Immunostaining for matrix metalloproteinases 1, 2, and 3 was significantly more intense in corneas with keratoglobus than in normal controls. Matrix metalloproteinase staining intensity was especially prominent in areas where the underlying Bowman's layer was disrupted.

Conclusions  Histological features in our keratoglobus specimens are consistent with previous reports. The similarities in immunohistochemical labeling between keratoglobus and keratoconus suggest that these entities may share common mechanisms that are involved in stromal thinning.

Methods  Forty mitomycin C–treated filtering blebs excised for persistent leaks from 40 patients were examined histopathologically using hematoxylin-eosin, periodic acid–Schiff, Masson trichrome, and Alcian blue histochemical stains.

Results  Ninety percent of the leaking blebs contained epithelial-stromal domes with areas of acellular stroma covered by attenuated epithelium. Seventy-five percent of the blebs demonstrated varying degrees of fibrovascular repair growing from the bleb margin, either beneath or interdigitating with the acellular zone. A novel observation in 65% of specimens was Alcian blue–positive myxoid stroma at the interface between the fibrovascular proliferation and the epithelial-stromal dome. The association between the presence of fibrovascular proliferation and Alcian blue–staining myxoid stroma was significant by Fisher exact test (P = .002).

Conclusions  A desirable filtration bleb requires a sufficient reparative fibrovascular response to maintain an epithelial-stromal barrier to prevent leakage. Fibroblasts must lay down a continuous collagen-rich fibrous layer, rather than merely myxoid stroma, beneath the conjunctival epithelium to promote bleb stability. Surgical techniques and postsurgical care should aim to attain this desired outcome.

Methods  Dendrimeric nanoparticles loaded with carboplatin were prepared. Forty LHβ-Tag mice were randomly assigned into 4 groups and treated at 10 weeks of age. Each mouse received a single subconjunctival injection in one eye, and the opposite eye was left untreated as a control. Group 1 (high-dose nanoparticle carboplatin) received 37.5 mg/mL of nanoparticle carboplatin; group 2 (low-dose nanoparticle carboplatin) received 10 mg/mL of nanoparticle carboplatin; group 3 (conventional carboplatin) received 10 mg/mL of carboplatin in aqueous solution; and group 4 (phosphate-buffered saline) received phosphate-buffered saline. Mice were killed on day 22 after treatment. Eyes were serially sectioned, and retinal tumor burden was quantified by histopathologic analysis.

Results  Mean tumor burden in the treated eyes was significantly smaller compared with the untreated eyes in the same mice in both nanoparticle carboplatin groups (group 1, P = .02; group 2, P = .02) and the treated eyes in the conventional carboplatin group (group 1 vs group 3, P < .01; group 2 vs group 3, P = .01) and phosphate-buffered saline group (group 1 vs group 4, P < .01; group 2 vs group 4, P = .01). The untreated eyes in the high-dose nanoparticle carboplatin group showed significantly smaller tumor mass compared with the conventional carboplatin (P = .03) and PBS (P = .04) groups. No toxic effects were observed in any of the groups.

Conclusion  A single injection of subconjunctival nanoparticle carboplatin was effective in the treatment of transgenic murine retinoblastoma, with no associated toxic effects. The higher dose of subconjunctival nanoparticle carboplatin decreased the tumor burden in the contralateral eye.

Clinical Relevance  This model provides a basis to test carboplatin nanoparticles for the treatment of human retinoblastoma.