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Purpose To evaluate pneumatic vitreolysis (PVL) in eyes with vitreomacular traction (VMT) with and without full-thickness macular hole (FTMH). Design Two multicenter (28 sites) studies: a randomized clinical trial comparing PVL with observation (sham injection) for VMT without FTMH (Protocol AG) and a single-arm study assessing PVL for FTMH (Protocol AH). Participants Participants were adults with central VMT (vitreomacular adhesion was ≤3000 μm). In Protocol AG, visual acuity (VA) was 20/32 to 20/400. In Protocol AH, eyes had a FTMH (≤250 μm at the narrowest point) and VA of 20/25 to 20/400. Methods Pneumatic vitreolysis using perfluoropropane (C3F8) gas. Main Outcome Measures Central VMT release at 24 weeks (Protocol AG) and FTMH closure at 8 weeks (Protocol AH). Results From October 2018 through February 2020, 46 participants were enrolled in Protocol AG, and 35 were enrolled in Protocol AH. Higher than expected rates of retinal detachment and tear resulted in early termination of both protocols. Combining studies, 7 of 59 eyes (12% [95% CI, 6%–23%]; 2 eyes in Protocol AG, 5 eyes in Protocol AH) that received PVL developed rhegmatogenous retinal detachment (n = 6) or retinal tear (n = 1). At 24 weeks in Protocol AG, 18 of 23 eyes in the PVL group (78%) versus 2 of 22 eyes in the sham group (9%) achieved central VMT release without rescue vitrectomy (adjusted risk difference, 66% [95% CI, 44%–88%]; P Conclusions In most eyes with VMT, PVL induced hyaloid release. In eyes with FTMH, PVL resulted in hole closure in approximately one third of eyes. These studies were terminated early because of safety concerns related to retinal detachments and retinal tears.

To describe a case of vitreous seeding with tractional retinal detachment due to metastatic renal cell carcinoma (RCC) in a patient on systemic checkpoint inhibitors.Case Report.A 44-year-old Hispanic woman with a history of RCC with metastases to the lungs, adrenal glands, hilar lymph nodes, and peritoneum presented with a complaint of severe floaters and blurry vision of the right eye for two months. She was found to have dense, web-like vitreous opacities and a peripheral tractional retinal detachment of the right eye. We performed a pars plana vitrectomy, membrane peeling, endolaser, air-fluid exchange, gas injection, and vitreous biopsy. The vitreous and membranes were sent for cytology with stains including AE1/AE3, PAX-8, CK-7, CA-IX, AMACR, and S-100. Cytology revealed crowded groups of glandular cells, some in papillary like formations. Positive stains included AE1/AE3, PAX-8, CK-7, CA-IX, and AMACR.Cytology and pathology demonstrated that vitreous seeding of metastatic RCC without an ocular mass lesion. We hypothesize that the use of checkpoint inhibitors played a role in allowing for the atypical and previously unreported seeding of RCC to the vitreous.

Purpose Evaluate macular features on preoperative ocular coherence tomography as indicators of postoperative visual gain following vitrectomy for epiretinal membrane (ERM). Methods A retrospective chart review of 66 eyes that underwent vitrectomy with membrane and internal limiting membrane peeling for symptomatic ERM. Inclusion criteria required a pre-op visual acuity of at least 20/200 and minimum follow-up of 1 year. In addition, 31 of these eyes with complete 5-line raster pre-op ocular coherence tomography had segmentation analysis which included noncentral ERM to inner nuclear layer and ERM to outer plexiform layer measurements. Results Eyes with "domed" pre-op macular contour had a mean preoperative acuity of 20/70 and gained a mean 2.4 lines at one year, compared with those with "flat" or "depressed" macular contour, having a 20/60 mean preoperative acuity and 0.6 lines gained (P = 0.02). Changes for other ocular coherence tomography features examined were not statistically significant. Paracentral ERM to inner nuclear layer measurements had moderate correlation, whereas paracentral ERM to outer plexiform layer measurements had weak correlation with gain in visual acuity. Conclusion An inner macular-domed contour in eyes with ERM predicted better visual gain after vitrectomy with ERM and internal limiting membrane peeling compared with a flat or depressed contour.

To examine the incidence of complications after posterior vitreous detachment (PVD) through an extended follow-up period and to identify patient-specific factors associated with a greater incidence of complication.Multicenter, retrospective observational study.Eyes with acute PVDs between 2015 and 2019 were identified through the Vestrum Health database.Complications (vitreous hemorrhage, retinal break, and retinal detachment) were evaluated after acute PVD at presentation and throughout the 6 month follow-up period.Rate of complications throughout the 6 month follow-up period after PVD and odds of complications by patient-specific factors.A total of 9635 eyes were included. The rate of any complication was 25.0%, isolated vitreous hemorrhage was 13.1%, retinal breaks without detachment was 16.0%, and retinal detachment was 4.2%. The majority of each complication was noted at presentation; however, 8.0% of isolated vitreous hemorrhages, 19.2% of retinal breaks without detachment, and 25.8% of retinal detachments were first noted within the 6 month follow-up period. Men experienced a significantly higher rate of any complication than women (30.0% versus 21.7%, P0.001), as well as retinal breaks and retinal detachments at both presentation and within 6 month follow-up. Patients with pseudophakia experienced significantly higher rates of delayed retinal detachment than phakic eyes (odds ratio, 1.85 [1.13, 3.04], P = 0.01). Among eyes with lattice/peripheral retinal degeneration, 44.2% experienced any complication throughout the clinical course. The presence of a retinal break in the fellow eye and retinal detachment in the fellow eye was associated with a significantly increased rate of any complication at any time point (retinal break: P0.0001; retinal detachment: P = 0.02), as well as each individual complication within the 6 month follow-up period. Among eyes with vitreous hemorrhage at presentation, 42.0% had a concurrent or delayed retinal break and 10.5% had concurrent or delayed retinal detachments.A clinically significant proportion of PVD-related complications are detected late, warranting extended follow-up, especially in higher-risk groups such as men, pseudophakic eyes, eyes with lattice/peripheral retinal degeneration, and eyes with a history of retinal breaks or detachment in the fellow eye.Proprietary or commercial disclosure may be found after the references.

Importance Limited data exist on the real-world safety outcomes of patients with neovascular age-related macular degeneration treated with brolucizumab (Beovu). Objective To determine the real-world incidence of intraocular inflammation (IOI), including retinal vasculitis (RV) and/or retinal vascular occlusion (RO), for patients with neovascular age-related macular degeneration who underwent brolucizumab treatment. Additionally, potential risk factors associated with these adverse events were evaluated. Design, setting, and participants This cohort study included patients with neovascular age-related macular degeneration in the Intelligent Research in Sight (IRIS) Registry and Komodo Healthcare Map. Patients initiating and receiving 1 or more brolucizumab injections from October 8, 2019, to June 5, 2020, with up to 6 months of follow-up were included. Intervention Brolucizumab injections. Main outcome and measures Incidence of IOI (including RV) and/or RO and RV and/or RO and risk stratification for the identified risk factors. Results Of 10 654 and 11 161 included eyes (from the IRIS Registry and Komodo Health database, respectively), the median follow-up times were 97 and 95 days. Most eyes switched from another anti-vascular endothelial growth factor agent (9686 of 10 654 [90.9%] and 10 487 of 11 161 [94.0%], respectively), most commonly aflibercept (7160 of 9686 [73.9%] and 7156 of 10 487 [68.2%]), and most were from women (6105 of 10 654 [57.3%] and 6452 of 11 161 [57.8%]). The overall incidence of IOI and/or RO was 2.4% (255 of 10 654 eyes) and 2.4% (268 of 11 161 eyes) for the IRIS and Komodo groups, respectively, and RV and/or RO, 0.6% (59 of 10 654 eyes and 63 of 11 161 eyes), respectively. Patients with a history of IOI and/or RO in the 12 months before brolucizumab initiation had an increased observed risk rate (8.7% [95% CI, 6.0%-11.4%] and 10.6% [95% CI, 7.5%-13.7%]) for an IOI and/or RO event in the 6 months following the first brolucizumab treatment compared with patients without prior IOI and/or RO (2.0% in both data sets). There was an increased estimated incidence rate in women (2.9% [95% CI, 2.5%-3.3%] and 3.0% [95% CI, 2.6%-3.4%]) compared with men (1.3% [95% CI, 1.0%-1.7%] and 1.4% [95% CI, 1.0%-1.7%]), but this risk was not as large as that of a prior IOI and/or RO. Similar findings were observed for patients with RV and/or RO events. Conclusions and relevance The incidence rate of IOI and/or RO was approximately 2.4%. Patient eyes with IOI and/or RO in the 12 months prior to first brolucizumab injection had the highest observed risk rate for IOI and/or RO in the early months after the first brolucizumab treatment. However, given study limitations, the identified risk factors cannot be used as predictors of IOI and/or RO events, and causality with brolucizumab cannot be assessed.

To evaluate treatment patterns and outcomes of patients in the United States who received antivascular endothelial growth factor (anti-VEGF) agents for wet age-related macular degeneration (AMD).Retrospective study PARTICIPANTS: Patients with wet AMD.Using the Intelligent Research in Sight Registry, we studied patients with wet AMD who received ≥1 anti-VEGF injection, who were ≥50 years old, and with ≥1.5 years of follow-up. Patients were grouped based on follow-up duration (in years): ≥1.5 (cohort 1), ≥2.5 (cohort 2), and ≥3.5 (cohort 3).Patient characteristics were similar between treatment groups. 36.8%, 34.5%, and 39.2% of ranibizumab, aflibercept, and all anti-VEGF eyes, respectively, had an injection interval8 weeks in length at the end of year 1. Results were similar at year 2 and 3. In cohorts 1-3, visual acuity (VA) changes from baseline ranged from 0.3 to 0.7 (year 1), -1.3 to -1.7 (year 2), and -2.8 to -3.1 (year 3) Early Treatment Diabetic Retinopathy Study letters. By the end of year 3, 41%, 39%, and 42% of ranibizumab, aflibercept, and all anti-VEGF eyes, respectively, had discontinued treatment (no injection for6 months).Approximately one-third of eyes had injection intervals8 weeks in length at the end of year 1. VA was slightly better at the end of year 1 and declined after the first year despite treatment. By the end of year 3, more than one-third of eyes had discontinued treatment. Given the high treatment burden, wet AMD patients may benefit from more durable approaches that require less frequent dosing.

OBJECTIVE: To evaluate pneumatic vitreolysis (PVL) in eyes with vitreomacular traction (VMT) with and without full-thickness macular hole (FTMH). DESIGN: Two multi-center (28 sites) studies: one randomized clinical trial comparing PVL with observation (sham injection) for VMT without FTMH (Protocol AG), and a single-arm study assessing PVL for closure of FTMH (Protocol AH). PARTICIPANTS: Participants were adults with central VMT in which the vitreomacular adhesion was 3000 μm or less. In AG, visual acuity (VA) was 20/32 to 20/400. In AH, eyes had FTMH (≤250 μm at the narrowest point) and VA of 20/25 to 20/400. INTERVENTION: PVL using C(3)F(8) gas. MAIN OUTCOME MEASURES: Central VMT release without rescue treatment at 24 weeks (AG). FTMH closure without rescue treatment at 8 weeks (AH). RESULTS: From October 2018 to February 2020, 46 participants were enrolled in AG and 35 eligible participants were enrolled in AH. Higher than expected rates of retinal detachments and tears resulted in early termination of both protocols. Combining studies, 7 of 59 (12% [95% CI, 6%–23%]; 2 in AG, 5 in AH) eyes that received PVL developed rhegmatogenous retinal detachment (6) or retinal tear (1). At 24 weeks in AG, 18 of 23 eyes in the PVL group (78%) versus 2 of 22 eyes in the sham group (9%) had central VMT release without rescue vitrectomy (adjusted risk difference = 66% [95% CI, 44%–88%], P < .001). The mean change in VA letter score from baseline at 24 weeks in AG was 6.7 in the PVL group and 6.1 in the sham group (adjusted difference = −0.8 [95% CI, −6.1 to 4.5], P=.77; negative values indicate greater improvement in sham group). In AH,10 of 35 eyes (29% [95% CI, 16%–45%]) had FTMH closure without rescue vitrectomy at 8 weeks. The mean change in VA from baseline at 8 weeks in AH was −1.5 letters (95% CI, −10.3 to 7.3). CONCLUSIONS: In most eyes with VMT, PVL induced hyaloid release. In eyes with FTMH, PVL resulted in hole closure in approximately one third of eyes. These studies were terminated early because of safety concerns related to retinal detachments and retinal tears. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT03677869, NCT03647267

Here we present a case series of full thickness macular holes (FTMHs) that closed with topical medical therapy. We see this technique as a promising alternative to surgery, especially in small FTMHs with cystoid hydration.

Purpose To identify sustained differences in intraocular pressure (IOP) after intravitreous injections of anti–vascular endothelial growth factor (VEGF) drugs. Design Database study. Participants Patients seeing an ophthalmic provider who contributes to the database. Methods We identified a total of 23 776 unique patients who received only a single type of anti-VEGF medication (bevacizumab, aflibercept, or ranibizumab) by injection in the right eye in the American Academy of Ophthalmology Intelligent Research in Sight Registry. Subgroups included patients with age-related macular degeneration only and patients who had not received an anti-VEGF injection for at least 1 year before the study. We examined those with at least 12, 18, and 25 injections for each of these 3 medications. For all groups, we used fellow, untreated eyes for comparison. Main Outcome Measures The mean change in IOP from baseline at a minimum of 1 year of follow-up and the proportion of eyes with a clinically significant IOP increase (defined as sustained rise of at least 6 mmHg to an IOP of more than 21 mmHg). Results All patients in all groups receiving all drugs showed a decrease in IOP from baseline, with a mean of 0.9 mmHg in treated eyes compared with an average decrease of 0.2 mmHg in fellow untreated eyes, a statistically significant difference. A generalized linear model accounting for confounders associated bevacizumab with slightly less lowering of IOP than aflibercept and ranibizumab in most subgroups. A clinically significant IOP increase was seen in 2.6% of eyes receiving injections compared with 1.5% in the associated untreated fellow eyes. Clinically significant IOP increases occurred at a rate of 1.9%, 2.8%, and 2.8% for aflibercept, ranibizumab, and bevacizumab, respectively, which was significantly higher than untreated fellow eyes for bevacizumab and ranibizumab, but not for aflibercept. Conclusions These analyses from real-world data indicate that anti-VEGF intravitreous injections are associated with a small but statistically significant decrease in IOP over time. A proportion of patients, on average 2.6%, experienced a sustained clinically significant IOP rise with these drugs overall compared with 1.5% in the fellow untreated eyes. However, such an increase was not seen with aflibercept.

IMPORTANCE: Because variation in care on weekends has been reported in many surgical fields, it is of interest if variations were noted for care patterns of rhegmatogenous retinal detachments (RRDs). OBJECTIVE: To assess the association between modality of RRD repair and day of the week that patients receive a diagnosis or undergo RRD repair. DESIGN, SETTING, AND PARTICIPANTS: A retrospective claims-based cohort analysis was performed of primary RRD surgery for 38 144 commercially insured patients in the United States who received a diagnosis of incident RRD between January 1, 2008, and December 31, 2016, and underwent repair within 14 days of diagnosis. Multinomial regression models were used to assess patients’ likelihood of repair with different modalities, logistic regression models were used to assess patients’ likelihood of reoperation, and linear regression models were used to assess time from diagnosis to repair. Data analysis was performed from March 9 to September 5, 2019. EXPOSURES: Day of the week that the patient received a diagnosis of RRD or underwent RRD repair. MAIN OUTCOME AND MEASURES: Modality of repair, time from diagnosis to repair, and 30-day reoperation rate. RESULTS: Among the 38 144 patients in the study (23 031 men [60.4%]; mean [SD] age at diagnosis, 56.8 [13.4] years), pneumatic retinopexy (PR) was more likely to occur when patients received a diagnosis of RRD on Friday (relative risk ratio [RRR], 1.37; 95% CI, 1.17-1.60), Saturday (RRR, 1.73; 95% CI, 1.36-2.20), or Sunday (RRR, 1.53; 95% CI, 1.08-2.17) compared with Wednesday. Pneumatic retinopexy was more likely to be used for surgical procedures on Friday (RRR, 1.55; 95% CI, 1.33-1.80), Saturday (RRR, 2.03; 95% CI, 1.61-2.56), Sunday (RRR, 2.28; 95% CI, 1.55-3.35), or Monday (RRR, 1.70; 95% CI, 1.46-1.98). Patients undergoing PR on Sundays were more likely to receive another procedure (PR, scleral buckle, or pars plana vitrectomy) within 30 days (odds ratio, 1.62; 95% CI, 1.07-2.45). An association between the need for reoperation for repairs performed via scleral buckle or pars plana vitrectomy and the day of the week of the initial repair was not identified. Patients who received a diagnosis on a Friday waited a mean of 0.28 days (95% CI, 0.20-0.36 days) longer for repair than patients who received a diagnosis on a Wednesday. CONCLUSIONS AND RELEVANCE: These findings suggest that management of RRD varies according to the day of the week that diagnosis and repair occurs, with PR disproportionately likely to be used to repair RRDs during the weekend. Ophthalmologists should be aware that these results suggest that patients undergoing PR on Sundays may be more likely to require reoperation within 30 days.

To identify sustained differences in intraocular pressure (IOP) after intravitreous injections of anti-vascular endothelial growth factor (VEGF) drugs.Database study.Patients seeing an ophthalmic provider who contributes to the database.We identified a total of 23 776 unique patients who received only a single type of anti-VEGF medication (bevacizumab, aflibercept, or ranibizumab) by injection in the right eye in the American Academy of Ophthalmology Intelligent Research in Sight Registry. Subgroups included patients with age-related macular degeneration only and patients who had not received an anti-VEGF injection for at least 1 year before the study. We examined those with at least 12, 18, and 25 injections for each of these 3 medications. For all groups, we used fellow, untreated eyes for comparison.The mean change in IOP from baseline at a minimum of 1 year of follow-up and the proportion of eyes with a clinically significant IOP increase (defined as sustained rise of at least 6 mmHg to an IOP of more than 21 mmHg).All patients in all groups receiving all drugs showed a decrease in IOP from baseline, with a mean of 0.9 mmHg in treated eyes compared with an average decrease of 0.2 mmHg in fellow untreated eyes, a statistically significant difference. A generalized linear model accounting for confounders associated bevacizumab with slightly less lowering of IOP than aflibercept and ranibizumab in most subgroups. A clinically significant IOP increase was seen in 2.6% of eyes receiving injections compared with 1.5% in the associated untreated fellow eyes. Clinically significant IOP increases occurred at a rate of 1.9%, 2.8%, and 2.8% for aflibercept, ranibizumab, and bevacizumab, respectively, which was significantly higher than untreated fellow eyes for bevacizumab and ranibizumab, but not for aflibercept.These analyses from real-world data indicate that anti-VEGF intravitreous injections are associated with a small but statistically significant decrease in IOP over time. A proportion of patients, on average 2.6%, experienced a sustained clinically significant IOP rise with these drugs overall compared with 1.5% in the fellow untreated eyes. However, such an increase was not seen with aflibercept.

Purpose To describe the experience of authors using intravitreal bevacizumab (IVB) for eyes with recurrent vitreous hemorrhage (VH) after vitrectomy for proliferative diabetic retinopathy. Methods Chart review was performed on eligible eyes from the Illinois Retina Associates' patient database that had at least 6 months of follow-up after receiving IVB in the operative eye for recurrent VH after vitrectomy for proliferative diabetic retinopathy. Results Twelve eyes of nine patients were included in the study and none required repeat vitrectomy for recurrent VH. Mean follow-up was 22 months (range, 8-42). A mean of 8.1 IVB (range, 1-18) were given. The mean number of recurrent VH was 4 (range, 2-8), and a mean of 3.5 of these VHs (range, 1-8) were clear at the appointment after an injection, typically in 4 to 6 weeks. Patients with history of multiple recurrent VH received prophylactic IVB, and repeated injections at regular intervals were associated with increased time period without recurrent VH. Conclusion Intravitreal bevacizumab was a safe and effective adjunct in this series for the management of recurrent VH after vitrectomy for proliferative diabetic retinopathy. No patients required repeat vitrectomy for recurrent VH, and prophylactic IVB was associated with longer periods of clear vitreous in the late postoperative period.

Importance The determination of optical coherence tomography (OCT) central subfield thickness (CST) is an objective measure, and visual acuity (VA) is a subjective measure. Therefore, using OCT CST changes as a surrogate for VA changes in diabetic macular edema seems reasonable. However, studies suggest that change in OCT CST following anti–vascular endothelial growth factor (anti-VEGF) treatment for diabetic macular edema is correlated with changes in VA but varies substantially among individuals, and so may not be a good surrogate for changes in VA. Objective To determine associations between changes in VA and changes in OCT CST across 3 anti-VEGF agents (aflibercept, bevacizumab, or ranibizumab) used in a randomized clinical trial for diabetic macular edema. Design, Setting, and Participants Post hoc analyses were conducted of DRCR Retina Network Protocol T among 652 of 660 participants (98.8%) meeting inclusion criteria for this investigation. The study was conducted between August 22, 2012, and September 23, 2015. The post hoc data collection and analysis were performed from May 29 to July 11, 2018. Interventions Six monthly intravitreous anti-VEGF injections (unless success was achieved after 3-5 months) were administered; subsequent injections or focal/grid laser photocoagulation treatments were given as needed per protocol to achieve stability. Main Outcomes and Measures Association between changes in VA letter score with changes in CST at 12, 52, and 104 weeks after randomization to aflibercept, bevacizumab, or ranibizumab. Results Of the 652 participants, 304 were women (46.6%); median age was 61 years (interquartile range, 54-67 years). The correlation between CST and VA at the follow-up visits was 0.24 (95% CI, 0.16-0.31) in 616 patients at 12 weeks, 0.31 (95% CI, 0.24-0.38) in 609 patients at 52 weeks, and 0.23 (95% CI, 0.15-0.31) in 566 patients at 104 weeks. The correlation coefficients of change in VA vs change in OCT CST for these time intervals were 0.36 (95% CI, 0.29-0.43) at 12 weeks, 0.36 (95% CI, 0.29-0.43) at 52 weeks, and 0.33 (95% CI, 0.26-0.41) at 104 weeks. Conclusions and Relevance Changes in CST appear to account for only a small proportion of the total variation in changes in VA. These findings do not support using changes in OCT CST as a surrogate for changes in VA in phase 3 clinical trials evaluating anti-VEGF for diabetic macular edema or as a guide to inform the physician or patient about changes in VA after anti-VEGF treatment. Trial Registration ClinicalTrials.gov identifier:NCT01627249

Here, we present an observational case report of choroidal involvement of subcutaneous diffuse large B-cell lymphoma (DLBCL). An 85-year-old female presented with a growing mass on her left abdominal wall that had been gradually growing over 2 months, which was diagnosed as subcutaneous DLBCL. A total of 1.5 months after her initial diagnosis, she presented with decreased peripheral vision of her right eye with intermittent pain for 1 month, and nausea and dizziness for 3 days. A large choroidal mass with vitreous seeding was found and vitreous aspiration with flow cytometry established the diagnosis of intraocular DLBCL. No tumorous lesions were detected anywhere else. Therefore, the patient was diagnosed as stage IV subcutaneous DLBCL with solely intraocular involvement, and was subsequently treated with systemic and intravitreal chemotherapy. A total of 9 months later, she achieved complete remission. It was concluded that subcutaneous extranodal DLBCL is a very rare form of non-Hodgkin lymphoma that can involve only the choroid.

Objective To evaluate the anatomic and visual outcomes after a surgical procedure for displacement of thick submacular hemorrhage in patients with age-related macular degeneration. Design Retrospective, noncomparative, interventional case series. Participants Twenty-nine consecutive eyes of 28 patients with thick submacular hemorrhage secondary to age-related macular degeneration. Intervention The procedure consisted of a pars plana vitrectomy with subretinal recombinant tissue plasminogen activator injection (125 mg/ml) through a translocation microcannula, followed by fluid–air exchange and postoperative prone positioning. Main outcome measures Intraoperative and postoperative surgical complications, preoperative and postoperative best-corrected visual acuities, postoperative fluorescein angiography results, and additional postoperative treatments. Results Total subfoveal blood displacement was achieved in 25 eyes, with subtotal displacement in the others. Based on fluorescein angiography results, 8 eyes were eligible for additional postoperative treatments. At 3 months, 17 eyes had gained more than 2 lines of visual acuity, whereas 3 had lost more than 2 lines. The difference between preoperative and 3-month postoperative visual acuity was statistically significant ( P = 0.0167). Complications consisted of 2 cases of vitreous hemorrhage that cleared within 4 weeks. Conclusions This surgical technique seems useful in displacing thick submacular hemorrhage secondary to age-related macular degeneration, allowing postoperative fluorescein angiography testing and, potentially, subsequent treatments. No significant complication from the procedure was identified. However, further controlled studies will be required to assess its efficacy in the management of this difficult clinical problem.

Genetic testing can make a very positive impact on individuals and families affected with inherited eye disease in a number of ways. When properly performed, interpreted, and acted on, genetic tests can improve the accuracy of diagnoses and prognoses, can improve the accuracy of genetic counseling, can reduce the risk of disease occurrence or recurrence in families at risk, and can facilitate the development and delivery of mechanism-specific care. However, like all medical interventions, genetic testing has some specific risks that vary from patient to patient. For example, the results of a genetic test can affect a patient's plans to have children, can create a sense of anxiety or guilt, and can even perturb a patient's relationships with other family members. For these reasons, skilled counseling should be provided to all individuals who undergo genetic testing to maximize the benefits and minimize the risks associated with each test.

Purpose To report a case of central serous chorioretinopathy caused by the use of spironolactone, a competitive antagonist of aldosterone. Methods Case report and review of the literature. Results A 26-year-old white woman on Aldactone (spironolactone) for the treatment of acne and Adderall (dextroamphetamine/amphetamine) for the treatment of attention deficit hyperactivity disorder, developed central serous chorioretinopathy, which resolved upon discontinuation of spironolactone and remitted after restarting it. Conclusion It is likely that spironolactone use contributed to the development of central serous chorioretinopathy in this patient. Concomitant use of amphetamine may also have played a role.

Purpose: The purpose of the study is to evaluate a recent series of patients who presented with open-globe injuries and to compare this series with a previous series collected at the authors' institution to determine whether prognostic factors or visual outcomes have changed. Methods: A retrospective review of 290 eyes of consecutive patients who presented to the Wilmer Ophthalmological Institute with open-globe injuries between December 1985 and January 1993 (group B) was compared with a series of 476 eyes with openglobe injury treated and evaluated at this institute between January 1970 and December 1981 (group A). For comparison, the outcomes evaluated included rates of enucleation and final visual acuity. Results: Several factors identified previously in group A to correlate with visual outcomes also were found to correlate significantly ( P P = 0.02). The incidence of enucleation was lower in group B (24%) than in group A (30%). However, the percentage of patients who achieved ambulatory visual acuity (5/200) or better was similar in both groups (57%, group A versus 55%, group B). Conclusion: Prognostic factors identified previously proved valid in this recent series. Visual outcomes have improved at this institution in the last 20 years for patients with severe ocular trauma, although visual potential for these patients is still limited.

Purpose: An inferior peripheral iridectomy (IPI) was used to prevent forward migration of silicone oil in vitrectomized eyes; however, in approximately one third of eyes, the IPI closed spontaneously. Occlusion of the IPI by fibrin is believed to be an early event in permanent IPI closure by scar tissue. The authors determined whether intraocular tissue plasminogen activator (tPA) would restore and maintain IPI Patency in eyes that had early occlusion of the IPI by fibrin. Methods: Between November 1993 and January 1995,12 patients who underwent vitrectomy with silicone tamponade and IPI for complicated retinal detachment received an anterior chamber injection of tPA (6.25 or 12.5 μg) for occlusion of the IPI by fibrin. Results: All 12 patients had lysis of fibrin and maintained a patent IPI at the last follow-up (124 ± 95 days). One patient required multiple tPA injections for recurrent fibrin formation. In another patient, a small hyphema developed after the tPA injection, which did not occlude the IPI. When compared with the natural course in a very similar group of patients previously reported, tPA had a statistically significant beneficial effect in the maintenance of IPI Patency ( P = 0.040). Conclusions: Intraocular tPA can be safely used to lyse postoperative fibrin occluding the IPI in eyes with silicone oil tamponade. Early lysis of this fibrin maintains IPI patency.

BACKGROUND AND OBJECTIVE: To compare the Optomap imaging system (Optos PLC, Dunfermline, Scotland) with conventional fundus photography in patients with cytomegalovirus (CMV) retinitis. PATIENTS AND METHODS: Patients treated at Rush University for acquired immune deficiency syndrome and CMV retinitis were studied prospectively. Conventional nine-field photography and Optomap ultra-wide–field photography were performed on the same day. A patient satisfaction questionnaire was completed. The main outcome measures were total retinal area imaged, area of CMV retinitis imaged, and patient satisfaction. RESULTS: Twelve eyes met the inclusion criteria. Ultra-wide–field imaging captured 48.3% greater retinal area and 40.0% greater CMV retinitis area compared with standard photography. Standard photography missed peripheral CMV lesions in two eyes. The patient satisfaction survey indicated a preference for ultra-wide–field imaging based on increased comfort and decreased imaging time. CONCLUSION: The ultra-wide–field Optomap imaging system tended to capture greater areas of total retina and peripheral CMV retinitis lesions. Patients tended to prefer ultra-wide–field imaging because of the perceived time requirements and comfort of use. [Ophthalmic Surg Lasers Imaging 2010;41:311–315.]

The authors report the clinicopathologic features of an unusually aggressive form of histiocytosis X (Langerhans' cell histiocytosis) in a 36-year-old man who presented with diplopia and early development of pituitary failure from presumed involvement of the hypothalamus. Results of postmortem examination showed infiltrates of histiocytes and mixed inflammatory cells, with a variably dense desmoplastic tissue within the orbit and sclera bilaterally, the left optic nerve, choroid, emissary canals, and many other body systems including the pituitary, heart, lung, and gastrointestinal tract. Diagnosis was confirmed by immunohistochemical staining of large histiocytes within diseased areas, with anti-T6 and anti-S-100 antibodies.

Purpose To present best-corrected visual acuity (BCVA) findings and other clinical outcomes from eyes of patients enrolled in one of the Submacular Surgery Trials (SST) evaluating surgical removal versus observation of predominantly hemorrhagic subfoveal choroidal neovascularization (CNV) associated with age-related macular degeneration. Design Randomized clinical trial (SST Group B Trial). Participants Eligible patients had subfoveal choroidal neovascular lesions greater than 3.5 disk areas (8.9 mm2) composed of at least 50% blood (either blood or CNV underlying the center of the foveal avascular zone) and BCVA of 20/100 to light perception in the study eye. Intervention Patients were assigned randomly at time of enrollment to observation or surgical removal of blood and any associated CNV. Main outcome measure A successful outcome was defined a priori as either improvement in visual acuity (VA), no change in VA, or a decline in VA of no more than 1 line (7 letters) from baseline to the 24-month examination based on an intent-to-treat analysis. Results Of 336 patients enrolled, 168 were assigned to each treatment arm; treatment arms were balanced by baseline characteristics. Of 1501 expected examinations 3 months through 36 months after baseline, 1370 (91%) were performed. Loss of > or =2 lines (> or =8 letters) of VA occurred in 56% of surgery eyes, versus 59% of observation eyes examined at 24 months. Although severe loss of VA was not the primary outcome of interest, surgery more often prevented such loss: 36% in the observation arm versus 21% in the surgery arm at the 24-month examination (chi2 P = 0.004). Of initially phakic eyes, the cumulative percentage that had undergone cataract surgery by 24 months was 44% in the surgery arm, compared with 6% in the observation arm. Twenty-seven eyes (16%) in the surgical arm, compared with 3 eyes (2%) in the observation arm, had a rhegmatogenous retinal detachment (RD). Conclusions Submacular surgery as performed in the SST Group B Trial did not increase the chance of stable or improved VA (the primary outcome of interest) and was associated with a high risk of rhegmatogenous RD, but did reduce the risk of severe VA loss in comparison with observation. This article contains additional online-only material available at http://www.ophsource.com/periodicals/ophtha.

To evaluate the anatomic and visual outcomes after a surgical procedure for displacement of thick submacular hemorrhage in patients with age-related macular degeneration.Retrospective, noncomparative, interventional case series.Twenty-nine consecutive eyes of 28 patients with thick submacular hemorrhage secondary to age-related macular degeneration.The procedure consisted of a pars plana vitrectomy with subretinal recombinant tissue plasminogen activator injection (125 micrograms/ml) through a translocation microcannula, followed by fluid-air exchange and postoperative prone positioning [correction].Intraoperative and postoperative surgical complications, preoperative and postoperative best-corrected visual acuities, postoperative fluorescein angiography results, and additional postoperative treatments.Total subfoveal blood displacement was achieved in 25 eyes, with subtotal displacement in the others. Based on fluorescein angiography results, 8 eyes were eligible for additional postoperative treatments. At 3 months, 17 eyes had gained more than 2 lines of visual acuity, whereas 3 had lost more than 2 lines. The difference between preoperative and 3-month postoperative visual acuity was statistically significant (P = 0.0167). Complications consisted of 2 cases of vitreous hemorrhage that cleared within 4 weeks.This surgical technique seems useful in displacing thick submacular hemorrhage secondary to age-related macular degeneration, allowing postoperative fluorescein angiography testing and, potentially, subsequent treatments. No significant complication from the procedure was identified. However, further controlled studies will be required to assess its efficacy in the management of this difficult clinical problem.

Purpose: To study the outcome of open globe injuries In patients aged Methods: Between January 1970 and January 1993, 180 eyes of children who presented with an open globe injury were retrospectively analyzed. Patients were divided into two groups. One group of children underwent treatment of an open globe injury between January 1970 and December 1981 (group A) and another between December 1985 and January 1993 (group B). Main outcome measures studied were final visual acuity and enucleation rates. Risk factors studied included age, race, sex, visual acuity, type of trauma, and various injury characteristics at presentation. Results: The factors associated with visual outcomes included: age, type of injury, wound size, initial visual acuity, and retinal detachment. Final visual outcome and enucleation rates were not significantly different between the older series (group A) and the recent series (group B). Lenticular damage, location, posterior extent of the injury, and presence of an intraocular foreign body had been significant prognostic factors in the older series, but were not statistically associated with the prognosis in the recent series. Conclusion: The nature of the injury and the patient's age are the main determining factors in the outcome of open globe injuries in children. Journal of Pediatric Ophthalmology and Strabismus 2001;38:72-77.

Purpose Resistance to antiviral therapy is a potential cause of progression of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome. We investigated the results of viral sensitivity testing in a series of patients with clinically resistant retinitis who had positive results of blood or urine cytomegalovirus cultures. Methods All patients with newly diagnosed cytomegalovirus retinitis between January 1990 and December 1991 were prospectively studied. Blood and urine cultures for cytomegalovirus were obtained in a nonrandomized subgroup of this group. The results of in vitro sensitivity to foscarnet and ganciclovir, determined by a DNA hybridization assay, were then analyzed in seven patients with clinically resistant cytomegalovirus retinitis and whose blood or urine culture results, or both, were positive for cytomegalovirus while on a treatment regimen. Results Foscarnet-resistant cytomegalovirus (ID 50 > 300 μM) was isolated from two patients, one of whom was being treated with foscarnet. Ganciclovir-resistant cytomegalovirus (ID 50 > 6.0 μM) was isolated from four patients, three of whom were being treated with ganciclovir. Foscarnet- and ganciclovir-resistant cytomegalovirus occurred with previous ganciclovir therapy in one patient. Clinical improvement occurred in three patients whose change in therapy was based on viral sensitivity testing. In general, prolonged therapy with one drug was associated with a progressive increase in the ID 50 for that drug. Conclusions Viral resistance to foscarnet or ganciclovir may explain refractory cytomegalovirus retinitis in some patients.

Endothelins (ETs) are a family of potent vasoactive peptides present in the eye. In the rabbit eye, both ET-1 and ET-3 are present in high concentrations in the iris and ciliary body and in lower concentrations elsewhere. Forty-eight hours after injection of 2.5 micrograms of ET-1 and ET-3 into the anterior vitreous of conscious rabbits, intraocular pressure was reduced by 43% and 45%, respectively, and did not return to normal for at least 5 days. The decrease in intraocular pressure was not due to increased aqueous outflow and was not prevented by pretreatment with indomethacin. Injection of either ET-1 or ET-3 (2.5 to 10 micrograms) into the anterior chamber or posterior vitreous cavity resulted in marked vasoconstriction, which was initiated within seconds and persisted for greater than 4 hours. Both endothelins potently constricted the pupil when added to freshly excised rabbit anterior segments. Endothelins are therefore potential participants in the local regulation of intraocular pressure, ocular blood vessel tone, and iris smooth muscle tone and may be important mediators in ocular pathologic conditions. Endothelins at pharmacologic doses may be useful in the control of intraocular pressure or blood flow.

Carboxypeptidase E (CPE), also referred to as enkephalin convertase or carboxypeptidase H (EC 3.4.17.10), is present in neurotransmitter secretory granules and can remove C-terminal basic residues following endopeptidase cleavage during peptide processing. Using in situ hybridization with 35S-labeled oligonucleotide probes, we have mapped the localization of CPE mRNA in the rat brain. Specificity for CPE was confirmed by control experiments, which included production of identical patterns hybridization with 3 different antisense oligonucleotide probes, loss of label with RNase pretreatment of sections or co-incubation with excess unlabeled probe, and lack of labeling with sense orientation probes. In addition, the regional distribution of CPE mRNA by Northern blot analysis corresponded with distribution of labeling by in situ hybridization. The highest levels of CPE mRNA were found to be present in the pyramidal cells of the hippocampus, the pituitary anterior and intermediate lobes, the ependymal cells of the lateral ventricle, the endopiriform nucleus, the basolateral amygdala, the supraoptic nucleus, and the paraventricular nucleus. Intermediate levels were present in the thalamus, medial geniculate nucleus, lateral septal nucleus, piriform and entorhinal cortex, nucleus of the tractus solitarius, cerebellar cortex, pontine nuclei, and inferior olive. The lowest levels were found in the hippocampal granule cell layer, lateral hypothalamus, globus pallidus, and brain stem reticular formation. Ibotenic acid lesions of the hippocampus eliminated the majority of the label, which had been present over pyramidal cells, though labeling was increased over areas of reactive gliosis, suggesting that activated astrocytes can also synthesize CPE mRNA. In general, the localization of CPE mRNA in the rat brain corresponded to the distribution of enkephalin and other peptide neurotransmitter-synthesizing neurons, though CPE mRNA was also present in neurons that do not secrete known peptides and in reactive glia. The widespread yet specific localization of CPE mRNA in the rat brain suggests it may be an excellent marker for peptide synthesizing cells in the CNS.

We have explored the cellular loci of endothelin (ET) actions and formation in the brain, using cerebellar mutant mice as well as primary and continuous cell cultures. A glial role is favored by several observations: (i) mutant mice lacking neuronal Purkinje cells display normal ET receptor binding and enhanced stimulation by ET of inositolphospholipid turnover; (ii) in weaver mice lacking neuronal granule cells, ET stimulation of inositolphospholipid turnover is not significantly diminished; (iii) C6 glioma cells and primary cultures of cerebellar astroglia exhibit substantial ET receptor binding and ET-induced stimulation of inositolphospholipid turnover; (iv) ET promotes mitogenesis of C6 glioma cells and primary cerebellar astroglia; and (v) primary cultures of cerebellar astroglia contain ET mRNA. ET also appears to have a neuronal role, since it stimulates inositolphospholipid turnover in primary cultures of cerebellar granule cells, and ET binding declines in granule cell-deficient mice. Thus, ET can be produced by glia and act upon both glia and neurons in a paracrine fashion.

Background The ganciclovir implant (Vitrasert; Bausch & Lomb Inc, Claremont, Calif) has been a useful device in the management of cytomegalovirus retinitis. Seven months after placement, implant exchange is often considered. However, removal may be difficult and may result in vitreous hemorrhage or intraocular dislocation. Objective To describe a suture loop attached to the implant strut and left in the sub–Tenon space to aid in implant removal. Methods Twenty-five eyes of 17 patients received a ganciclovir implant with an 8-0 nylon suture loop left beneath the Tenon capsule and underwent at least 6 months of follow-up. Two of these eyes subsequently had a similarly modified ganciclovir implant placed at a separate site (inferonasally) with at least 6 additional months of follow-up. Six eyes of 3 patients had the implant removed as part of an exchange and underwent at least 4 months of follow-up. Results In the 25 eyes, there were no cases of endophthalmitis, wound leak, suture exposure, or other complications. At implant removal in the 6 eyes previously mentioned, the loop was used for traction on the implant and aided in localization of the implant strut. In these 6 eyes, there were no cases of retinal or choroidal detachment, visually significant vitreous hemorrhage, implant dislocation, or other complications. Conclusion A sub–Tenon capsule suture loop is well tolerated and can assist in ganciclovir implant removal.

Common emergent scenarios - recommended guidelines for timing of ophthalmologic and other specialized evaluation the epidemiology of ocular trauma - a preventable ocular emergency ocular evaluation evaluation of paediatric ocular trauma radiographic and echographic imaging studies timing guidelines for emergent surgery preoperative preparation and anaesthesia injuries of the lid and lacrimal system orbital trauma infection of the lacrimal system, eyelids and orbit ocular and periocular inflammatory syndromes ocular burns non-infectious disorders of the conjunctiva and cornea infectious conjunctivitis and keratitis corneoscleral lacerations and ruptures injuries of the anterior segment.

Purpose: Endothelins (ETs) are a family of vasoconstrictive peptides produced in part by vascular endothelial cells. They are synthesized in the eye, particularly in the uveal tract, and can markedly constrict the iris and preretinal vessels in the rabbit eye. Two ET receptor subtype families have been characterized and cloned, termed ETAand ETB. To better understand the distribution of ocular ET receptors, we localized ET receptor-binding sites in human and rabbit eyes. Method: Autoradiography with iodine 125-labeled ET-1 and varying concentrations of unlabeled ET-3 was used to localize ET receptor-binding subtypes in the posterior pole of human and rabbit eyes. Results: The ETA-like receptor-binding sites are localized to the retinal and choroidal blood vessels, whereas the ETB-like receptor-binding sites are localized to the neural and glial substance of the retina. Conclusions: Endothelin receptor-binding subtypes are differentially located in the posterior pole of human and rabbit eyes. Endothelin peptides released within the retina and choroid may participate in the ocular manifestations of a variety of systemic disorders, including systemic hypertension.

mRNAs for isozymes of phospholipase C (PLC) were localized in rat brain by in situ hybridization with oligonucleotide probes for PLC isozymes I, II, and III of Rhee's group [Suh, P.-G., Ryu, S. H., Moon, K. H., Suh, H. W. & Rhee, S. G. (1988) Proc. Natl. Acad. Sci. USA 85, 5419-5423 and (1988) Cell 54, 161-169], and isozyme I of Bennett and Crooke [Bennett, C. F., Balcarek, J. M., Varrichio, A. & Crooke, S. T. (1988) Nature (London) 334, 268-270], which we designate PLC-A. The isozymes displayed different localizations. PLC-A mRNA was highest in the mitral cell layer of the olfactory bulb, choroid plexus, hippocampus and dentate gyrus, magnocellular hypothalamic nuclei, rostral raphe nuclei, and cerebellar Purkinje cells. PLC-I was highest in the internal granular cell layer of the olfactory bulb, cerebral cortex, caudate, nucleus of the lateral olfactory tract, reticular nucleus of thalamus, hippocampus and dentate gyrus, and granule cell layer of the cerebellum. PLC-II had a more widespread distribution, with relatively high levels in the internal granular layer of the olfactory bulb, hippocampus and dentate gyrus, and cerebellar Purkinje and granule cells. PLC-III label was low throughout the brain. These distributions suggest selective coupling of individual PLC isozymes with particular postsynaptic receptors. PLC-A may be preferentially associated with 5-hydroxytryptamine 1C receptors, vasopressin V1 receptors, and a subtype of glutamate receptors. PLC-I may be linked to muscarinic m1 and m3 receptors as well as other receptors. The distribution of PLC-II mRNA resembles that of src protooncogene, with which it displays sequence homology.

Endothelin (ET) is a recently identified vasoactive peptide with three isoforms for which three genes have been cloned. The cellular sites of synthesis of this peptide have not yet been identified in vivo. Using Northern blot analysis, we have detected two forms of ET mRNA in rat tissues: a 3.7-kilobase form in the kidney, eye, and brain, a 2.5-kilobase form in the intestine, and both forms in the lung. We have localized these forms of ET mRNA in several rat tissues using in situ hybridization. In the 19-day rat fetus, ET mRNA is highest in the lung, intestine, and meninges. At high resolution, ET mRNA is localized in the lung to respiratory epithelial cells of bronchioles and apparently in blood vessels. In adult tissues, ET mRNA is present throughout the lung, in the renal medulla vasa recta, and in the iris of the eye. ET mRNA is synthesized in close proximity to ET binding sites in many organs (e.g., lung, kidney, intestine, and eye), suggesting a local action of this peptide. However, in other areas (e.g., heart and renal cortex), ET binding sites are present in the absence of ET mRNA, suggesting an action of ET from the bloodstream or from neurons. Northern blot analysis of ET mRNA in microvascular endothelial cells in culture indicates that ET is synthesized in small blood vessels and regulated similarly to its regulation in large vessels. Our results provide evidence that ET, like other regulatory peptides, may serve in several tissues as a neuromodulator or local hormone.