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To investigate the association of the Affordable Care Act (ACA) with nationwide eye-related emergency department (ED) use.Retrospective, cross-sectional study.All patients who presented to the ED with an eye-related primary diagnosis were eligible for inclusion.Nationally representative data from the US Nationwide Emergency Department Sample were used to analyze eye-related ED visits before (2010-2013) and after (2014-2017) the ACA was mandated. All ED visits were categorized as emergent or nonemergent or could not be determined.The primary outcome was to compare the nationwide and regional incidence of eye-related ED visits per 100 000 US population before (2010-2013) and after (2014-2017) the ACA was mandated. Secondary outcome measures included change in payor status, proportion of urgent versus nonurgent visits, proportion of visits at teaching versus nonteaching hospitals, associated charges, and discharge disposition.A total of 16 808 343 eye-related ED visits occurred in the United States during the study period from 2010 to 2017. Of these, 8 088 203 ED visits occurred before the ACA was mandated (2010-2013), and 8 720 766 ED visits occurred after the ACA was mandated (2014-2017). After the ACA was mandated in 2014, there was an initial decline in incidence of eye-related ED visits from 652.4 per 100 000 population in 2013 to 593.0 per 100 000 population in 2014, followed by a rapid increase in incidence to 658.5 per 100 000 population in 2015, with a further increase to 746.6 per 100 000 population in 2016. The percentage of uninsured patients decreased from 19.0% to 14.3%. The increase in ED use was greatest for individuals in the lowest income quartile (895.1 per 100 000 population in 2013 to 964.0 per 100 000 in 2017). Overall, 44.8% of ED visits were due to nonemergent eye conditions.Although the ACA increased insurance coverage for Americans, theoretically increasing access to outpatient ophthalmic care, this did not decrease ED reliance for management of ophthalmic conditions. Additional measures beyond expanding insurance coverage may be necessary to provide high-quality, efficient, and equitable outpatient ophthalmic care to all Americans.

Purpose To investigate the underlying reason for the previously observed impact of baseline lesion size, number, and circularity on geographic atrophy (GA) growth rate. Design Retrospective analysis of a multicenter, prospective, randomized controlled trial. Participants Age-Related Eye Disease Study participants with GA secondary to nonexudative age-related macular degeneration. Methods We manually delineated atrophic lesions on color fundus photographs of 318 eyes with GA followed up over at least 2 visits (mean follow-up duration, 5.1 ± 3.0 years). We calculated GA area growth rate for each eye based on the first and last visit. GA perimeter-adjusted growth rate was defined as the ratio between GA area growth rate and mean GA perimeter between the first and last visit for each eye. Main Outcome Measures GA area growth rate, growth rate of the square root of GA area, and GA perimeter-adjusted growth rate. Results GA area growth rate was correlated strongly with mean GA perimeter (r2 = 0.66). GA area growth rate was associated with baseline GA area (r2 = 0.39; P Conclusions The growth rate of GA area is associated strongly with lesion perimeter. This relationship explains the previously observed influences of baseline GA size, lesion number, and circularity on GA growth rate. GA perimeter-adjusted growth rate is uncorrelated with the 3 morphologic factors and may serve as a surrogate outcome measure to monitor GA progression in future studies.

Topic Determining the natural history of unifocal versus multifocal geographic atrophy (GA) secondary to nonexudative age-related macular degeneration. Clinical Relevance The association between GA focality (i.e., unifocal vs. multifocal lesions) and enlargement rate is inconsistent in the literature. Some studies report a comparable growth rate between unifocal and multifocal GA, whereas others suggest the growth rate varies widely between the 2 groups. Methods We searched 5 literature databases up to May 3, 2019, for studies that classified treatment-naive GA patients based on lesion focality. We performed a random effects meta-analysis to determine the growth rates of GA. To account for different entry times among cohorts, we introduced a horizontal translation factor to the dataset of each cohort. Heterogeneity and study quality were assessed using the I2 statistic and Quality in Prognosis Studies tool, respectively. Publication bias was evaluated by funnel plots and the Egger test. Results We included 12 studies with 3489 eyes from 3001 patients. After the introduction of translation factors, the effective radius of unifocal and multifocal GA enlarged linearly over approximately 7 years. The effective radius growth rate of multifocal GA (0.199±0.012 mm/year) was 46.3% higher than the growth rate of unifocal GA (0.136±0.008 mm/year; P 2 and 3 ). This difference disappeared after we accounted for different baseline total perimeters between unifocal and multifocal groups. The measured GA growth rate was consistent across studies using color fundus photography, fundus autofluorescence, or OCT (P = 0.35–0.99). Conclusions The effective radius of GA enlarges linearly and steadily over time in both unifocal and multifocal GA. The lesion focality is a significant prognostic factor for the GA effective radius growth rate. We propose that the growth rate of GA area is directly proportional to the total lesion perimeter (a measure of the number of retinal pigment epithelium cells exposed at the lesion border). Additional studies are needed to understand the cellular mechanisms underlying this relationship.

Purpose To evaluate the association between Medicaid expansion and diabetic dilated eye examinations. Design A retrospective difference in differences (DiD) analysis using individual-level survey response data from January 1, 2009, to December 31, 2017. Participants A total of 52 392 survey responses from 50 states and the District of Columbia between 2009 and 2017. Responders were adults aged 18 to 64 years reporting a previous diagnosis of diabetes and a household income below 138% of the US federal poverty line (FPL). Methods The Centers for Disease Control and Prevention’s Behavioral Risk Factor Surveillance System data were used to identify survey responders who were asked about the presence of dilated eye examinations from years before and after Medicaid expansion implementation. Main Outcome Measures The DiD in proportion of dilated eye examinations among diabetic persons aged 18 to 64 years with household incomes below 138% of the FPL between states that did and did not implement Medicaid expansion. Results Implementation of Medicaid expansion policies was associated with a 1.3% (95% confidence interval [CI], −3.8 to 6.4; P = 0.61), 6.3% (95% CI, 1.3–11.3; P = 0.016), 4.1% (95% CI, −0.8 to 9.0; P = 0.11), and 2.3% (95% CI, −1.6 to 6.2; P = 0.23) increase in the proportion of diabetic persons aged 18 to 64 years with incomes below 138% of the FPL receiving a dilated eye examination within the past year due to Medicaid expansion 1, 2, 3, and 4 cumulative years after expansion, respectively. Conclusions Medicaid expansion policies were significantly associated with an increase in dilated eye examination rates within the first 2 years after implementation. However, this increase did not persist beyond this period, with nonsignificant increases 3 and 4 cumulative years after implementation. Healthcare policymakers should be aware that additional measures beyond expanding insurance coverage may be necessary to increase and sustain the rate of dilated eye examinations among diabetic populations.

Patients with a history of pan retinal photocoagulation for proliferative diabetic retinopathy underwent ultra-widefield imaging with identification of the long ciliary nerve. This study found high prevalence of photocoagulation along the nerve despite current guidance. Proliferative diabetic retinopathy is a prevalent disease associated with significant morbidity, reduced quality of life, high costs, and significant visual loss. 1 Panretinal photocoagulation (PRP) is a widely-used technique to decrease neovascularization and bleeding and reduce severe vision loss in proliferative diabetic retinopathy (PDR). 2 , 3 Despite its uses, multiple cases have linked peripheral laser photocoagulation near the long ciliary nerve (LCN) to corneal ulceration, transient accommodative paresis and pupillary disturbances 4 , 5 , 6 . Current guidelines from the Basic and Clinical Science Course recommend that “the long ciliary nerves in the 3 o’clock and 9 o’clock meridians should be avoided” during PRP. 7 The development of ultra-widefield (UWF) fundus imaging offers a unique opportunity to visualize the long ciliary nerve. The aim of this study is to establish the frequency of inadvertent panretinal photocoagulation along the long ciliary nerve through confirmation of laser marks on widefield fundus imaging.

Topic Systematic review and meta-analysis of the natural history of autosomal recessive Stargardt disease (STGD1). Clinical Relevance Controversy exists regarding the progression pattern of atrophic lesions secondary to STGD1, and the reported growth rates vary widely among studies. Methods We searched in 6 literature databases up through March 15, 2019, to identify studies that monitored atrophy progression by fundus autofluorescence in untreated eyes with STGD1 for 6 months or more. We analyzed both study- and individual-level data from the included studies using 3 models: the area linear model (ALM), radius linear model (RLM), and area exponential model (AEM), in which the area, radius, and natural log–transformed area changes linearly with time, respectively. A horizontal translation factor was added to each dataset to correct for different participants’ entry times into the studies. The best model was determined by the predicted age of lesion onset and dependence of growth rates on baseline lesion sizes. The risk of bias was assessed using the Newcastle-Ottawa scale. Results Of 3158 articles screened, 7 studies (564 eyes) met our inclusion criteria. Cumulative study- and individual-level datasets fit along a straight line in the RLM after introducing horizontal translation factors to correct for different entry times (r2 = 0.99 and r2 = 0.93, respectively). The growth rate of effective lesion radius was 0.104 mm/year (95% confidence interval, 0.086–0.123 mm/year). The age of atrophy onset predicted by the RLM (22.7±5.0 years) was comparable to the reported age at onset of symptoms (22.1±3.1 years); in contrast, the predictions by the ALM and AEM deviated from this number by more than 5 years. Based on the individual-level data, the effective radius growth rate was independent of the baseline lesion size (r = 0.06); in comparison, the growth rates of area and natural log-transformed area were significantly dependent on the baseline lesion size (r = 0.47 and r = –0.33, respectively). Conclusions The progression of STGD1 lesions followed the RLM in both study- and individual-level data. The effective radius growth rate of atrophic lesions could serve as a reliable outcome measure to monitor STGD1 progression.

Topic Systematic review and meta-analysis of how fellow eye status predicts the progression rate of geographic atrophy (GA). Clinical Relevance The status of age-related macular degeneration (AMD) in the fellow eye has been used as an indicator of the GA progression rates in primary eyes, but the reported growth rates vary widely in prior clinical studies. Methods We searched MEDLINE, EMBASE, Cochrane Library, Clinicaltrials.gov , and PubMed up to September 12, 2018, for studies that classified treatment-naive GA patients based on different AMD manifestations in the fellow eyes and that monitored GA progression in the primary eyes. Three fellow eye statuses were analyzed: (1) no GA or choroidal neovascularization (CNV) in the fellow eye, (2) GA in the fellow eye, and (3) CNV in the fellow eye. To account for the patients’ different entry times, we introduced a horizontal translation factor to shift each dataset within each group. We determined the translation factor by adjusting it 1 month at a time until the r2 in weighted least squares regression (r2WLS) was maximized for the cumulative linear trend line of all datasets. Heterogeneity and study quality were assessed using the I2 statistic and Newcastle–Ottawa scale, respectively. Publication bias was evaluated by funnel plots, the Egger test, and the Begg test. Results We included 9 studies with 2134 eyes from 1835 patients. After the introduction of translation factors, the datasets in each fellow eye group fit along a straight line with a high r2WLS. The GA radius growth rate in fellow eyes with GA (0.179±0.003 mm/year) and fellow eyes with CNV (0.159±0.015 mm/year) was significantly higher than that in fellow eyes without GA or CNV (0.110±0.009 mm/year; P Conclusions We confirmed that the presence of advanced AMD in the fellow eye, defined as GA or CNV, can serve as a biomarker of the GA enlargement rate in the primary eye. This may assist the design of clinical trials and may shed light on the natural history of GA expansion.

We have reported previously that retinal pigment epithelium (RPE) differentiated from induced pluripotent stem cells (iPSC) generated from fibroblasts of patients with age-related macular degeneration (AMD) exhibit a retinal degenerative disease phenotype and a distinct transcriptome compared to age-matched controls. Since the genetic composition of the iPSC and RPE are inherited from fibroblasts, we investigated whether differential behavior was present in the parental fibroblasts and iPSC prior to differentiation of the cell lines into RPE. Principal component analyses revealed significant overlap (essentially no differences) in the transcriptome of fibroblasts between AMD and controls. After reprogramming, there was no significant difference in the transcriptome of iPSC generated from AMD versus normal donors. In contrast, the transcriptome of RPE derived from iPSC segregated into two distinct clusters of AMD-derived cells versus controls. Interestingly, mitochondrial dysfunction in AMD-derived RPE was evident after approximately two months in culture. Moreover, these differences in mitochondrial dysfunction were not evident in the parental fibroblasts and iPSC. This study demonstrates an altered transcriptome and impaired mitochondrial function in RPE derived from AMD patients versus controls, and demonstrates these differences are not present in the original fibroblasts or iPSC. These results suggest that pathology in AMD is triggered upon differentiation of parent cells into RPE. More study of this phenomenon could advance the current understandings of the etiology of AMD and the development of novel therapeutic targets.

Summary Background Since they were first derived more than three decades ago, embryonic stem cells have been proposed as a source of replacement cells in regenerative medicine, but their plasticity and unlimited capacity for self-renewal raises concerns about their safety, including tumour formation ability, potential immune rejection, and the risk of differentiating into unwanted cell types. We report the medium-term to long-term safety of cells derived from human embryonic stem cells (hESC) transplanted into patients. Methods In the USA, two prospective phase 1/2 studies were done to assess the primary endpoints safety and tolerability of subretinal transplantation of hESC-derived retinal pigment epithelium in nine patients with Stargardt's macular dystrophy (age >18 years) and nine with atrophic age-related macular degeneration (age >55 years). Three dose cohorts (50 000, 100 000, and 150 000 cells) were treated for each eye disorder. Transplanted patients were followed up for a median of 22 months by use of serial systemic, ophthalmic, and imaging examinations. The studies are registered with ClinicalTrials.gov, numbers NCT01345006 (Stargardt's macular dystrophy) and NCT01344993 (age-related macular degeneration). Findings There was no evidence of adverse proliferation, rejection, or serious ocular or systemic safety issues related to the transplanted tissue. Adverse events were associated with vitreoretinal surgery and immunosuppression. 13 (72%) of 18 patients had patches of increasing subretinal pigmentation consistent with transplanted retinal pigment epithelium. Best-corrected visual acuity, monitored as part of the safety protocol, improved in ten eyes, improved or remained the same in seven eyes, and decreased by more than ten letters in one eye, whereas the untreated fellow eyes did not show similar improvements in visual acuity. Vision-related quality-of-life measures increased for general and peripheral vision, and near and distance activities, improving by 16–25 points 3–12 months after transplantation in patients with atrophic age-related macular degeneration and 8–20 points in patients with Stargardt's macular dystrophy. Interpretation The results of this study provide the first evidence of the medium-term to long-term safety, graft survival, and possible biological activity of pluripotent stem cell progeny in individuals with any disease. Our results suggest that hESC-derived cells could provide a potentially safe new source of cells for the treatment of various unmet medical disorders requiring tissue repair or replacement. Funding Advanced Cell Technology.

Dysfunction and eventual loss of retinal pigment epithelial (RPE) cells is a hallmark of atrophic age-related macular degeneration (AMD), and linked to oxidative and nitrosative damage. Herein, we use a high-throughput screen (HTS) to identify compounds that protect human RPE cells from oxidative stress-induced cell death and elucidate the possible mechanism of action. HTS was used to identify compounds that protect RPE cells from oxidative damage. We tested the identified compound(s) in models of RPE stress, including tert-butyl hydroperoxide (TBHP) exposure, ultraviolet-B (UV-B)-mediated light damage and nitrosative stress to the basement membrane using ARPE-19 cells, primary human RPE cells and induced-pluripotent stem cell (iPSC)-derived RPE cells from patients with AMD. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect gene expression of oxidative stress- and apoptosis-related genes and mitochondrial function was measured using a Seahorse XF96 analyzer to elucidate possible mechanisms of action. Five thousand and sixty-five compounds were screened, and of these, 12 compounds were active based on their ability to improve cell viability after exposure to TBHP. After chemical structure review, we identified ciclopirox olamine as a potent inhibitor of oxidative damage to RPE cells. Ciclopirox olamine increased cell viability in ARPE-19 cells treated with TBHP, UV-B light or on nitrite-modified extracellular matrix (ECM) by 1.68-fold, 1.54-fold and 4.3-fold, respectively (p < 0.01). Treatment with TBHP altered expression of genes related to oxidative stress and apoptosis, which was reversed by pretreatment with ciclopirox olamine. Ciclopirox olamine improved mitochondrial function in TBHP-exposed ARPE-19 cells and iPSC-derived RPE cells. Ciclopirox olamine protected primary human RPE cells and iPSC-derived RPE cells from the oxidative stress or damaged basement membrane. HTS of bioactive Food and Drug Administration (FDA)-approved libraries and follow-up studies can be used to identify small molecules (including ciclopirox olamine) that protect RPE cells exposed to various stressors associated with disease progression of AMD. This strategy can be used to identify potential compounds for treatment and prevention of AMD.

Objective To determine the effect of lens status upon the anatomic and visual results in primary diabetic vitrectomy. Design Retrospective, comparative, consecutive case series. Participants One hundred two eyes of 85 patients with proliferative diabetic retinopathy and its complications that underwent primary vitrectomy. Methods The eyes that remained phakic after vitrectomy were compared with the eyes that were either aphakic or pseudophakic (nonphakic) postoperatively. Main Outcome Measures Intraoperative and postoperative complications, vitreoretinal reoperation rate, and ultimate anatomic and visual success with at least 6 months' follow-up. Results Preoperatively, 72 eyes were phakic, and 30 were aphakic (n = 1) or pseudophakic (n = 29). During vitrectomy, 1 eye underwent lensectomy and 12 eyes underwent phacoemulsification with lens implantation. Postoperatively, 59 eyes were phakic and 43 eyes were nonphakic. The vitreoretinal reoperation rate was significantly higher ( P = 0.04) for the phakic group (28.8%) than for the nonphakic group (11.6%). Rubeosis iridis developed in 3 phakic eyes and no nonphakic eyes ( P = 0.26). Intraoperative complications were similar in the phakic and nonphakic groups ( P = 0.40). Postoperative complications such as rhegmatogenous retinal detachment ( P = 0.39), nonclearing vitreous hemorrhage ( P = 0.07), and anterior chamber complications ( P = 0.60) were also similar. Visual acuity improved by at least 0.2 logarithm of the minimum angle of resolution units in 76.2% of the phakic eyes and 86.0% of the nonphakic eyes ( P = 0.22). Conclusions Eyes that were phakic after primary diabetic vitrectomy had a significantly higher subsequent vitreoretinal reoperation rate when compared with nonphakic eyes, suggesting that diabetic eyes are less likely to require additional vitreoretinal surgery if they are rendered nonphakic before or during vitrectomy.

Purpose To report macular hole formation among siblings within four families. Design Observational case series. Methods Four families were identified who had macular holes among siblings from within three multiphysician tertiary-care referral retina practices. Results In the first family, two sisters in their seventh decade developed Stage 2 macular holes requiring surgical intervention; two male siblings were unaffected. In a second family, three of four siblings were affected, including one brother with a Stage 4 macular hole, one sister with a Stage 3 macular hole, and a third sister with a lamellar macular hole. In a third family, two siblings (one man, one woman) developed macular holes within 1 year of each other. Three years later, the male sibling developed a macular hole in the fellow eye. In the last family, twin sisters developed macular holes (unilateral in one sister, bilateral in the other), and their deceased father may also have had bilateral macular holes. Conclusions The occurrence of macular holes in these four sets of siblings suggests a possible genetic component in the formation of macular holes in these individuals.

Purpose To explore the use of adult human photoreceptor transplantation as a treatment for advanced retinitis pigmentosa (RP). Design Prospective noncomparative case series. Participants Eight patients with advanced RP. Intervention Transplantation of adult human cadaver photoreceptor sheets harvested with the excimer laser. No immunosuppression was used postoperatively. Patients were followed for 12 months postoperatively. Main outcome measure Visual acuity and retinal function measured by psychophysical, electrophysiologic, and clinical testing. Results Best-corrected visual acuity (Bailey-Lovie chart), median reading speed, contrast sensitivity, and visual fields for the operated eye were not statistically significantly improved postoperatively. The amplitude and latency of the maculoscope electroretinogram, as well as the log threshold for dark adaptation, did not change between the operated and control (unoperated) eye. There was no detectable homograft reaction on slit-lamp biomicroscopy or fluorescein angiography. The only adverse effect observed was one patient who complained of monocular diplopia after retinal transplantation and subsequent cataract surgery. Conclusions Allogeneic adult human photoreceptor transplantation is feasible in RP but was not associated with rescue of central vision or a delay in visual loss. However, any possible slowing in the rate of retinal degeneration will take many years to determine.

PURPOSE: To report the histopathology after retinal pigment epithelial cell transplantation and subfoveal membranectomy in age-related macular degeneration. METHODS: An 85-year-old white woman with bilateral choroidal neovascularization underwent subfoveal membranectomy combined with transplantation of a sheet of human adult retinal pigment epithelium (retinal pigment epithelium) under the foveal center in the right eye. The patient was immunosuppressed postoperatively with prednisone, cyclosporine, and azathioprine. The patient died from congestive heart failure 114 days after surgery. RESULTS: A patch of hyperpigmentation was visible at the transplant site under the foveola after surgery. Mound-like clusters of individual round, large densely pigmented cells were present in the subretinal space and outer retina in this area. There was loss of the photoreceptor outer segments and native retinal pigment epithelium in the center of the transplant bed, with disruption of the outer nuclear layer predominantly over regions of multilayered pigmented cells. Cystic spaces were present in the inner and outer retina. A residual intra-Bruchs membrane component of the original choroidal neovascular complex was present under the transplant site. CONCLUSIONS: The transplant site contained clusters of round, pigmented cells that did not form a uniform monolayer in most areas. The morphology at the transplant site is consistent with the lack of visual improvement seen after surgery in this patient.

Drusen are subretinal pigment epithelial deposits that are characteristic of but not uniquely associated with age-related macular degeneration (AMD). Age-related macular degeneration is associated with two types of drusen that have different clinical appearances and different prognoses. Hard drusen appear as small, punctate, yellow nodules and can precede the development of atrophic AMD. Areolar atrophy of the retinal pigment epithelium (RPE), choriocapillaris, and outer retina develop as the drusen disappear, but drusen can regress without evidence of atrophy. Soft drusen appear as large (usually larger than 63 microm in diameter), pale yellow or grayish-white, dome-shaped elevations that can resemble localized serous RPE detachments. They tend to precede the development of clinically evident RPE detachments and choroidal neovascularization. Drusen characteristics correlated with progression to exudative maculopathy include drusen number (five or more), drusen size (larger than 63 microm in diameter), and confluence of drusen. Focal hyperpigmentation in the macula and systemic hypertension also are associated with an increased risk of developing choroidal new vessels (CNVs). Large drusen are usually a sign of diffuse thickening of Bruch's membrane with basal linear deposit, a vesicular material that probably arises from the RPE, constitutes a diffusion barrier to water-soluble constituents in the plasma, results in lipidization of Bruch's membrane, and creates a potential cleavage plane between the RPE basement membrane and the inner collagenous layer of Bruch's membrane through which CNVs can grow. Disappearance of drusen spontaneously and in areas adjacent to laser photocoagulation scars was first noted by Gass (Gass JD: Arch Ophthalmol 90:206-217, 1973; Trans Am Acad Ophthalmol Otolaryngol 75:580-608, 1971). Subsequent reports have confirmed these observations. Photocoagulation-induced drusen regression might prevent patients with drusen from developing exudative maculopathy. The mechanism for spontaneous drusen regression probably involves RPE atrophy. The mechanism for photocoagulation-induced drusen regression is unknown. If photocoagulation-induced drusen regression is anatomically similar to atrophy-associated drusen regression, then the former will be associated with dissolution of basal linear deposit and a residuum of basal laminar deposit. Sarks and coworkers (Sarks JP, Sarks SH, Killingsworth MC: Eye 11:515-522, 1997) proposed that this in turn will eliminate the potential cleavage plane between the RPE basement membrane and inner collagenous layer of Bruch's membrane through which CNVs grow, thus retarding the growth of CNVs.

Objective This study aimed to report the visual outcome of surgical removal of extensive peripapillary choroidal neovascularization (CNV) due to presumed ocular histoplasmosis syndrome (POHS). Design Retrospective review of the records of all patients seen at the Barnes Retina Institute who underwent surgical removal of extensive peripapillary CNV associated with POHS and who had at least 12 months of follow-up. Participants Seventeen consecutive eyes (in 14 patients) undergoing surgical removal of extensive peripapillary CNV associated with POHS were studied. Intervention Pars plana vitrectomy and surgical removal of CNV were performed. Main outcome measurements Best-corrected Snellen visual acuity, funduscopic examination, and intravenous fluorescein angiography were obtained before surgery and at regular intervals after surgery. Results In 14 of 17 eyes, the peripapillary CNV was subfoveal, and in 3 eyes, it was extrafoveal. All three eyes with extrafoveal CNV were not eligible for laser treatment according to Macular Photocoagulation Study guidelines because treatment would have spared less than 1.5 contiguous clock-hours of retina temporal to the optic disc. Follow-up ranged from 17 to 57 months, with a median of 32 months. In eyes with subfoveal CNV, best-corrected preoperative Snellen visual acuity ranged from 20/25 to counting fingers at 2 feet with a median of 20/200, and best-corrected final Snellen visual acuity ranged from 20/25 to 20/200 with a median of 20/40. In 7 (50%) of 14 eyes, a final Snellen acuity of 20/40 or better was achieved, and in all cases except 1, visual acuity improved or did not change with surgery. In the three eyes with extrafoveal CNV, best-corrected preoperative Snellen visual acuity ranged from 20/20 to 20/400 with a median of 20/200, and best-corrected final Snellen visual acuity was 20/20 in all cases. In addition, visual acuity improved with surgery. Conclusions The data from this small retrospective study suggest that surgical removal may provide visual benefit in selected cases of extensive peripapillary CNV due to POHS.

Purpose To determine the effects of the absence of the retinal pigment epithelium on the choriocapillaris and outer retina by performing retinal pigment epithelial cell debridement with mitomycin C to inhibit cell proliferation pharmacologically in the porcine eye. Methods A pars plana vitrectomy was performed in 12 eyes, and two neurosensory retinal detachments per eye were created by injecting 10 –3 mg/ml mitomycin C and 0.25% edetic acid into the subretinal space. Twenty minutes later, the retinal pigment epithelium was debrided, and the retina was reattached with a fluid-gas exchange. Results Bruch's membrane was devoid of native retinal pigment epithelium, and the choriocapillaris was patent immediately after debridement. No proliferation of the retinal pigment epithelium occurred 1 week after debridement, and choriocapillaris atrophy was present beneath areas of Bruch's membrane that were devoid of retinal pigment epithelium. Four weeks postsurgery, choriocapillaris atrophy persisted in all debrided blebs, although unpigmented retinal pigment epithelium repopulated portions of Bruch's membrane in one of three blebs. Outer retinal atrophy was present in areas of Bruch's membrane with no retinal pigment epithelium and no choriocapillaris 4 weeks postsurgery. The choriocapillaris was patent in areas of mitomycin C injection without debridement. Conclusion Absence of the retinal pigment epithelium leads to atrophy of the choriocapillaris within 1 week after surgery. This finding provides an animal model to study transplantation of retinal pigment epithelium onto bare patches of Bruch's membrane in age-related macular degeneration and other diseases and provides insight into the pathogenesis of nonexudative age-related macular degeneration.

Purpose: The purpose of the study is to identify the anatomic abnormalities associated with an absolute scotoma and the location and stability of fixation in patients with subfoveal neovascularization in age-related macular degeneration, presumed ocular histoplasmosis syndrome, and other disorders. Methods: Scanning laser ophthalmoscope microperimetry was superimposed on color fundus photographs and fluorescein angiograms of 21 eyes with subfoveal neovascular membranes secondary to age-related macular degeneration (14 eyes) and presumed ocular histoplasmosis syndrome (7 eyes). The authors determined the location and the area occupied by the absolute scotoma and each of the following subretinal lesions: subretinal hemorrhage, neurosensory retinal detachment, retinal pigment epithelial (RPE) atrophy, RPE hyperplasia, atrophy of the choriocapillaris, hard exudates, and the subfoveal neovascular membrane. The area of absolute scotoma determined by scanning laser ophthalmoscope microperimetry was superimposed on the anatomic lesions. The authors calculated the relative risk ratio (RR) of an absolute scotoma occurring in regions corresponding to each anatomic abnormality, and determined the preferred location and stability of fixation in each eye. Results: An absolute scotoma was present in areas of chorioretinal scar (RR = 107.61), RPE atrophy (RR = 9.97), subretinal hemorrhage (RR = 2.88), and the neovascular membrane (RR = 1.86). Fixation was stable in all patients with presumed ocular histoplasmosis syndrome but only 29% of patients with age-related macular degeneration. Fifty-five percent of patients with stable fixation fixated over an area of RPE hyperplasia. Conclusion: The relative risk of an absolute scotoma is highest over areas of chorioretinal scars, RPE atrophy, subretinal hemorrhage, and the neovascular membrane. Fixation is more stable in patients with subfoveal neovascularization from presumed ocular histoplasmosis syndrome than with age-related macular degeneration and frequently is present over an area of RPE hyperplasia.

Purpose To report a case of bilateral bull's-eye maculopathy in a patient who ingested uva ursi, a known inhibitor of melanin synthesis, for 3 years before the onset of symptoms. Design Observational case report. Methods Both eyes of a female patient were examined in the clinical practice setting. Results A 56-year-old woman who ingested uva ursi for 3 years noted a decrease in visual acuity within the past year. Ocular examination including fluorescein angiography revealed a typical bull's-eye maculopathy bilaterally. Conclusions Uva ursi is a known inhibitor of melanin synthesis. It is necessary to broaden the list of potential retinal toxic drugs to include herbal adjuvants such as Uva Ursi and to elicit a history of their use in patients with unexplained ocular findings.

OBJECTIVES: To discuss the current status of experimental studies on transplantation of the retinal pigment epithelium (RPE), and surgical results on the excision of subfoveal choroidal new vessel membranes in age-related macular degeneration (AMD) and presumed ocular histoplasmosis (POHS). STUDY DESIGN: Experimental study on transplantation of the RPE in organ culture and in vivo, and results of a prospective series on surgical excision of choroidal neovascularization. SETTING: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine. PATIENTS: Patients with subfoveal neovascular membranes secondary to AMD and POHS. MAIN OUTCOME MEASURES: Histological results on transplantation of the RPE onto Bruch's membrane in experimental animal models, and visual results on surgical excision of subfoveal choroidal neovascularization in patients with AMD and POHS. RESULTS: We have demonstrated that the RPE monolayer can heal after surgical debridement in the experimental animal, and retinal recovery occurs after healing of the RPE monolayer. We have demonstrated that RPE can reattach to healthy Bruch's membrane in vitro, and have performed RPE transplantation into the subretinal space in vivo. CONCLUSIONS: We are currently involved in a multifaceted approach aimed at RPE transplantation and surgical reconstruction of the photoreceptor-RPE-Bruch's membrane interface. We are hopeful that our approach will be applicable to the clinical problem of subfoveal choroidal new vessel membranes in AMD and POHS, in addition to the broad applicability of RPE transplantation to patients with diseases arising from primary RPE dysfunction.

Purpose To describe bilateral endogenous endophthalmitis caused by Ochrobactrum anthropi in a partially immunosuppressed patient who had undergone central venous access for hyperalimentation and home intravenous therapy. Methods Case report. Results Blood cultures were positive for O anthropi. Vitreous cultures grew a gram-variable bacillus. The patient's ocular and systemic condition markedly improved after intravitreal antibiotics and systemic ciprofloxacin. Conclusions Ochrobactrum anthropi may cause endogenous endophthalmitis in patients with a history of indwelling catheters for venous access or other permanent medical devices.

Purpose To describe two patients with uveitis who developed increased intraocular pressure that was unresponsive to maximum medical therapy eight and 13 months after periocular injection of triamcinolone acetonide. Methods Excised periocular tissue was analyzed for corticosteroid activity by gas chromatography and mass spectrometry. Results Excision of the periocular tissue, which contained visible triamcinolone acetonide, result' ed in a normal intraocular pressure within 14 days in both patients. Analysis of the excised tissue disclosed residual corticosteroid in one of the two patients. Conclusions Removal of periocular tissue containing injected corticosteroids may facilitate the management of patients developing increased intraocular pressure unresponsive to maximum medical therapy.

Purpose To improve visual function by retinal pigment epithelial (RPE) cell transplantation and systemic immunosuppression at the time of surgical removal of subfoveal choroidal neovascularization in exudative age-related macular degeneration (AMD). Design An interventional case series of RPE transplantation in exudative AMD. Methods Twelve patients (one eye only) underwent subfoveal membranectomy with transplantation of a sheet of adult human allogeneic RPE cells at a single institution and were followed for one year. Eligibility criteria included age >60, best-corrected acuity ≤20/63 and subfoveal neovascularization ≤9 disk areas on preoperative fluorescein angiography. All patients were started on triple immunosuppression postoperatively. The primary outcome measure was best-corrected vision, with contrast sensitivity and reading speed as secondary outcome measures. Results The best-corrected visual acuity ( P = .085), contrast sensitivity ( P = .204), and the reading speed ( P = .077) did not change significantly at one year compared with preoperative values. Transplants showed no signs of rejection in patients who were able to continue the immunosuppressants for six months. Postoperative surgical complications included cataract progression requiring surgery (three of eight phakic eyes), retinal detachment (three eyes), intraoperative retinal breaks (two eyes), and macular pucker (two eyes). None of the patients developed cystoid macular edema on postoperative fluorescein angiography or postoperative inflammation. Conclusions A sheet of adult human allogeneic RPE can be transplanted into the subretinal space in AMD patients at the time of subfoveal membranectomy. Systemic immune suppression appeared to prevent rejection of the transplanted tissue, but did not lead to an improvement in visual function.

Purpose To measure the wrinkling periodicity (peak-to-peak or trough-to-trough distance) for epiretinal membranes and contraction-induced choroidal folds, and use this data to infer differences in the elastic properties of the retina and choroid, respectively. Design Retrospective case review. Methods Forty eyes were identified with epiretinal membranes (33 eyes) or contraction-induced choroidal folds (seven eyes). Digital red-free photographs were used to determine the average peak-to-peak distance between adjacent folds of retina or choroid using commercially available software. Results The average peak-to-peak spacing was considerably larger for contraction-induced choroidal folds vs retinal folds caused by epiretinal membranes (278.2 ± 62.2 vs 82.2 ± 7.66 μm, respectively; P = .0001). There was no statistically significant correlation between the peak-to-peak distance and patient age for the epiretinal membrane group ( P = .25) or the choroidal folds group, although the age range of patients within the later group was narrow. Conclusions Epiretinal membranes and contraction-induced choroidal folds are two examples of wrinkling of biologic tissue under tangential stress. The larger peak-to-peak spacing for choroidal folds vs retinal folds demonstrates that the choroid is considerably stiffer than the retina under mechanical deformations.

ATP-dependent activation and deactivation of retinal rod outer segment phosphodiesterase is affected by calcium [Kawamura, S. and Bownds, M. D., J. Gen. Physiol. 77:571–591(1981)]. Our data demonstrate that although calmodulin has been found in rod outer segments [Liu, Y. P. and Schwartz, H., Biochim. Biophys. Acta 526:186–193(1978); Kohnken, R. E. et al , J. Biol. Chem. 256:12517–12522(1981)], this protein is not involved in calcium-dependent phosphodiesterase activation at light levels at which calcium clearly affects this enzyme's activity. Furthermore, calmodulin does not mediate the calcium-dependent deactivation of phosphodiesterase.

Seventy-nine eyes (61 patients) with open-angle glaucoma and uncontrolled intraocular pressure (IOP) of 23 mmHg or more despite maximal tolerated medical therapy and prior argon laser trabeculoplasty (75 eyes) were treated with neodymium: YAG (Nd: YAG) laser angle surgery and followed for at least 1 year. Ten pulses of 10 mJ were applied to the midtrabecular meshwork over 40 degrees in the most visible portion of the angle. The IOP was controlled successfully (less than or equal to 22 mmHg) in 60 eyes (76%) 1 month after treatment and in 36 of 78 eyes (46%) 1 year after treatment. Long-term complications included two eyes with advanced glaucoma that lost central fixation despite good IOP control after treatment.

Neodymium:YAG (Nd:YAG) and argon laser iridotomies were compared in a prospective, randomized clinical trial of 43 patients with bilateral chronic pupillary-block glaucoma. All patients had one eye randomly assigned to argon and the fellow eye assigned to Nd:YAG laser treatment. Follow-up ranged from 20 to 42 months. Iridotomy closure was not observed in Nd:YAG-treated eyes, but nine (21 %) argon iridotomies required retreatment. Visual loss due to progression of laser-induced lens or corneal damage was not observed in any eye. Nine (21 %) argon-treated eyes and eight (19%) Nd:YAG-treated eyes required laser trabeculoplasty for further intraocular pressure (IOP) lowering after iridotomy. Five (12%) argon-treated and two (5%) Nd:YAG-treated eyes required intraocular filtration surgery for long-term IOP control, but this difference was not statistically significant. There were no significant long-term differences between these treatment modalities.