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Purpose: To evaluate the completeness of conflict-of-interest self-reporting by ophthalmology researchers and to assess factors associated with self-reporting., Design: Cross-sectional observational study., Participants: We evaluated articles published between January and June 2017 in Ophthalmology, JAMA Ophthalmology, the American Journal of Ophthalmology, and Investigative Ophthalmology and Visual Science. To assess more accurately the cases in which an author published multiple articles, we defined a unit of analysis, authorship, for which each author of each article is a unique data point. To enable comparison with the Open Payments Database (OPD), we only included United States physician authorships., Methods: For each authorship, we defined self-reported relationships as the companies listed in the article's conflict-of-interest disclosures. Based on journal policies, we defined OPD-reported relationships as the list of companies that reported payments to the author within 36 months before submission., Main Outcome Measures: For each authorship, we assessed the proportion of OPD-reported relationships that were self-reported. The primary measurement was the proportion of authorships reporting none of their OPD-reported relationships., Results: Of the 660 total authorships (486 unique authors), 413 authorships (63%) reported none of their OPD-reported relationships, 112 (17%) reported some of them, 9 (1%) reported all of them, and 126 (19%) had 0 relationships. The proportion of authorships reporting none of their relationships did not differ significantly between journals that required reporting of all relationships compared with journals that required reporting only of relevant relationships (adjusted percentage, 61.4% vs. 64.3%; P = 0.46). Authorships with more dollars received during the reporting period showed higher rates of self-reporting (P < 0.001)., Conclusions: Even among journals that required complete reporting, self-reporting was low compared with an industry-maintained database of financial relationships. Deficiencies in reporting may undermine confidence in self-reporting and may compromise the transparency that is needed to interpret research results fairly., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Ocular coloboma is caused by failure of optic fissure closure during development and recognized as part of the microphthalmia, anophthalmia, and coloboma (MAC) spectrum. While many genes are known to cause colobomatous microphthalmia, relatively few have been reported in coloboma with normal eye size. Genetic analysis including trio exome sequencing and Sanger sequencing was undertaken in a family with two siblings affected with bilateral coloboma of the iris, retina, and choroid. Pathogenic variants in MAC genes were excluded. Trio analysis identified compound heterozygous donor splice site variants in CDON, a cell-surface receptor known to function in the Sonic Hedgehog pathway, c.928 + 1G > A and c.2650 + 1G > T, in both affected individuals. Heterozygous missense and truncating CDON variants are associated with dominant holoprosencephaly (HPE) with incomplete penetrance and Cdon-/- mice display variable HPE and coloboma. A homozygous nonsense allele of uncertain significance was recently identified in a consanguineous patient with coloboma and a second molecular diagnosis. We report the first compound heterozygous variants in CDON as a cause of isolated coloboma. CDON is the first HPE gene identified to cause recessive coloboma. Given the phenotypic overlap, further examination of HPE genes in coloboma is indicated., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: To assess the accuracy of macular spectral-domain OCT in detecting complete posterior vitreous detachment (PVD)., Design: Evaluation of diagnostic test or technology using a retrospective comparative study., Participants: One hundred seventy-five eyes in 175 patients (111 women and 64 men; mean age, 65 years) with preoperative OCT within 90 days of vitrectomy., Methods: Posterior vitreous detachment status on preoperative macular OCT was compared with PVD determination during vitrectomy. Attached vitreous was identified on OCT by visualizing the posterior vitreous cortex or premacular bursa. Complete PVD was identified by the absence of these findings and considered a positive outcome for the purpose of analysis., Main Outcome Measures: Sensitivity, specificity, positive predictive value, and negative predictive value of macular OCT for detection of complete PVD compared with findings at surgery., Results: Of the 38 eyes graded as showing complete PVD on OCT, 20 eyes were found to have pre-existing PVD at the time of surgery (true-positive results), and 18 eyes were found to have attached vitreous at the time of surgery (false-positive results). Of the 137 eyes graded as showing attached vitreous on OCT, 129 eyes had attached vitreous at the time of surgery (true-negative results), and 8 eyes had pre-existing PVD at the time of surgery (false-negative results). The sensitivity of OCT for detecting complete PVD was 71% and the specificity was 88%. In the study population, the positive predictive value of an OCT scan showing complete PVD was 53%, whereas the negative predictive value of an OCT scan showing attached vitreous was 94%., Conclusions: If the premacular bursa or posterior vitreous cortex are visualized on macular OCT, an accurate determination of attached vitreous can be made. The diagnosis of complete PVD by macular OCT is less accurate and requires ultrasound., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: We evaluated the Runge card, a near-vision eye chart designed for ease of use, by testing agreement in visual acuity results between it and the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart. As a clinical reference point, we compared the Runge card and an electronic Snellen chart with respect to agreement with ETDRS results., Methods: Participants consisted of adult eye clinic patient volunteers who underwent a protocol refraction, followed by testing with a Runge card, ETDRS chart, and Snellen chart. Mean logMAR visual acuities were calculated for each method. Agreement levels among the tests were assessed for the group overall and for subjects with good (ETDRS logMAR < 0.6; better than 20/80 Snellen equivalent) and poor (logMAR ≥ 0.6) acuity., Results: One hundred and thirty-eight participants completed testing. The mean ( ± standard deviation) logMAR visual acuities (Snellen equivalent) with Runge, ETDRS, and Snellen, respectively, were 0.66 ± 0.50 (20/91, n = 138), 0.59 ± 0.51 (20/78, n = 138), and 0.67 ± 0.62 (20/94, n = 137). Runge testing agreed similarly with ETDRS and Snellen testing, with CCC 0.92 between Runge and ETDRS, and 0.87 between Runge and Snellen (p = 0.14). Runge agreed better with ETDRS than Snellen agreed with ETDRS in participants with poor acuity (CCC = 0.79 vs. 0.63, respectively, p = 0.001) but not in those with good acuity (CCC = 0.70 vs. 0.87, respectively, p = 0.005)., Conclusion: Visual acuity measurements with the Runge near card agreed with measurements from the ETDRS to approximately the same degree as did the Snellen chart, suggesting potential utility of the Runge near card, particularly given its user-friendly characteristics and ease of use.

Importance: Clinical trial registries are intended to increase clinical research transparency by nonselectively identifying and documenting clinical trial designs and outcomes. Inconsistencies in reported data undermine the utility of such registries and have previously been noted in general medical literature., Objective: To assess whether inconsistencies in reported data exist between ophthalmic literature and clinical trial registries., Design, Setting, and Participants: In this retrospective, cross-sectional study, interventional clinical trials published from January 1, 2014, to December 31, 2014, in the American Journal of Ophthalmology, JAMA Ophthalmology, and Ophthalmology were reviewed. Observational, retrospective, uncontrolled, and post hoc reports were excluded, yielding a sample size of 106 articles. Data collection was performed from January through September 2016. Data review and adjudication continued through January 2017., Main Outcomes and Measures: If possible, articles were matched to registry entries listed in the ClinicalTrials.gov database or in 1 of 16 international registries indexed by the World Health Organization International Clinical Trials Registry Platform version 3.2 search engine. Each article-registry pair was assessed for inconsistencies in design, results, and funding (each of which was further divided into subcategories) by 2 reviewers and adjudicated by a third., Results: Of 106 trials that met the study criteria, matching registry entries were found for 68 (64.2%), whereas no matching registry entries were found for 38 (35.8%). Inconsistencies were identified in study design, study results, and funding sources, including specific interventions in 8 (11.8%), primary outcome measure (POM) designs in 32 (47.1%), and POM results in 48 (70.6%). In addition, numerous data pieces were unreported, including analysis methods in 52 (76.5%) and POM results in 38 (55.9%)., Conclusions and Relevance: Clinical trial registries were underused in this sample of ophthalmology clinical trials. For studies with registry data, inconsistency rates between published and registered data were similar to those previously reported for general medical literature. In most cases, inconsistencies involved missing data, but explicit discrepancies in methods and/or data were also found. Transparency and credibility of published trials may be improved by closer attention to their registration and reporting.

Purpose: The Rapid Access Vitreal Injection (RAVI) guide combines the function of an eyelid speculum and measuring caliper into a single instrument for assisting intravitreal injections. This study clinically evaluated the RAVI guide with respect to patient acceptance, complication rates, and operative goals., Methods: A prospective study was performed on 54 patients undergoing intravitreal injections using the RAVI guide (n = 32) or the speculum/caliper (n = 22). Device-related pain was assessed using the Wong-Baker scoring system, scaled from 0 (no pain) to 10 (agonizing pain)., Results: Mean device-related pain score did not differ significantly between the 2 groups, with scores of 0.6 and 0.7 for the RAVI guide and speculum groups, respectively. The rate of significant pain (score of ≥2) was twice as high in the speculum group (7 of 22, 32%) compared with the RAVI guide group (5 of 32, 16%), but this difference was not statistically significant (P = 0.19, Fisher's exact test). Operative goals of avoiding needle touch to lashes/lids and guiding needle insertion to the intended site were achieved in all patients., Conclusion: The RAVI guide appeared equivalent to the eyelid speculum in achieving operative goals, with similarly low pain scores. It has the potential for facilitating efficient, accurate, and safe intravitreal injections.

Purpose: We improved our understanding of central serous chorioretinopathy (CSC), we performed an analysis of noninvasive, high-resolution retinal imaging in patients with active and resolved CSC., Methods: Adaptive optics scanning light ophthalmoscopy (AOSLO) and spectral-domain optical coherence tomography (SD-OCT) were performed on five subjects with CSC. A custom AOSLO system was used to simultaneously collect confocal and split-detector images. Spectral domain-OCT volume scans were used to create en face views of various retinal layers, which then were compared to montaged AOSLO images after coregistration., Results: Three distinct types of intraretinal hyperreflective clusters were seen with AOSLO. These clusters had a well-demarcated, round, and granular appearance. Clusters in active CSC over areas of serous retinal detachment were termed type-1. They were found primarily in the outer nuclear layer (ONL) and were associated with large defects in the photoreceptor mosaic and ellipsoid zone. Clusters in areas where the retina had reattached were termed type-2. They also were located primarily in the ONL but showed stability in location over a period of at least 8 months. Smaller clusters in the inner retina along retinal capillaries were termed type-3., Conclusions: Retinal imaging in CSC using en face OCT and AOSLO allows precise localization of intraretinal structures and detection of features that cannot be seen with SD-OCT alone. These findings may provide greater insight into the pathophysiology of the active and resolved phases of the disease, and support the hypothesis that intraretinal hyperreflective foci on OCT in CSC are cellular in nature.

Purpose: Choroideremia is a progressive X-linked recessive dystrophy, characterized by degeneration of the retinal pigment epithelium (RPE), choroid, choriocapillaris, and photoreceptors. We examined photoreceptor structure in a series of subjects with choroideremia with particular attention to areas bordering atrophic lesions., Methods: Twelve males with clinically-diagnosed choroideremia and confirmed hemizygous mutations in the CHM gene were examined. High-resolution images of the retina were obtained using spectral domain optical coherence tomography (SD-OCT) and both confocal and non-confocal split-detector adaptive optics scanning light ophthalmoscope (AOSLO) techniques., Results: Eleven CHM gene mutations (3 novel) were identified; three subjects had the same mutation and one subject had two mutations. SD-OCT findings included interdigitation zone (IZ) attenuation or loss in 10/12 subjects, often in areas with intact ellipsoid zones; RPE thinning in all subjects; interlaminar bridges in the imaged areas of 10/12 subjects; and outer retinal tubulations (ORTs) in 10/12 subjects. Only split-detector AOSLO could reliably resolve cones near lesion borders, and such cones were abnormally heterogeneous in morphology, diameter and density. On split-detector imaging, the cone mosaic terminated sharply at lesion borders in 5/5 cases examined. Split-detector imaging detected remnant cone inner segments within ORTs, which were generally contiguous with a central patch of preserved retina., Conclusions: Early IZ dropout and RPE thinning on SD-OCT are consistent with previously published results. Evidence of remnant cone inner segments within ORTs and the continuity of the ORTs with preserved retina suggests that these may represent an intermediate state of retinal degeneration prior to complete atrophy. Taken together, these results supports a model of choroideremia in which the RPE degenerates before photoreceptors., Competing Interests: The authors have declared that no competing interests exist.

Purpose: The purpose of this study was to examine cone photoreceptor structure in retinitis pigmentosa (RP) and Usher syndrome using confocal and nonconfocal split-detector adaptive optics scanning light ophthalmoscopy (AOSLO)., Methods: Nineteen subjects (11 RP, 8 Usher syndrome) underwent ophthalmic and genetic testing, spectral-domain optical coherence tomography (SD-OCT), and AOSLO imaging. Split-detector images obtained in 11 subjects (7 RP, 4 Usher syndrome) were used to assess remnant cone structure in areas of altered cone reflectivity on confocal AOSLO., Results: Despite normal interdigitation zone and ellipsoid zone appearance on OCT, foveal and parafoveal cone densities derived from confocal AOSLO images were significantly lower in Usher syndrome compared with RP. This was due in large part to an increased prevalence of non-waveguiding cones in the Usher syndrome retina. Although significantly correlated to best-corrected visual acuity and foveal sensitivity, cone density can decrease by nearly 38% before visual acuity becomes abnormal. Aberrantly waveguiding cones were noted within the transition zone of all eyes and corresponded to intact inner segment structures. These remnant cones decreased in density and increased in diameter across the transition zone and disappeared with external limiting membrane collapse., Conclusions: Foveal cone density can be decreased in RP and Usher syndrome before visible changes on OCT or a decline in visual function. Thus, AOSLO imaging may allow more sensitive monitoring of disease than current methods. However, confocal AOSLO is limited by dependence on cone waveguiding, whereas split-detector AOSLO offers unambiguous and quantifiable visualization of remnant cone inner segment structure. Confocal and split-detector thus offer complementary insights into retinal pathology.

Purpose: To compare images of photoreceptor layer disruptions obtained with optical coherence tomography (OCT) and adaptive optics scanning light ophthalmoscopy (AOSLO) in a variety of pathologic states., Methods: Five subjects with photoreceptor ellipsoid zone disruption as per OCT and clinical diagnoses of closed-globe blunt ocular trauma (n = 2), macular telangiectasia type 2 (n = 1), blue-cone monochromacy (n = 1), or cone-rod dystrophy (n = 1) were included. Images were acquired within and around photoreceptor lesions using spectral domain OCT, confocal AOSLO, and split-detector AOSLO., Results: There were substantial differences in the extent and appearance of the photoreceptor mosaic as revealed by confocal AOSLO, split-detector AOSLO, and spectral domain OCT en face view of the ellipsoid zone., Conclusion: Clinically available spectral domain OCT, viewed en face or as B-scan, may lead to misinterpretation of photoreceptor anatomy in a variety of diseases and injuries. This was demonstrated using split-detector AOSLO to reveal substantial populations of photoreceptors in areas of no, low, or ambiguous ellipsoid zone reflectivity with en face OCT and confocal AOSLO. Although it is unclear if these photoreceptors are functional, their presence offers hope for therapeutic strategies aimed at preserving or restoring photoreceptor function.

Purpose: To describe photoreceptor structure and recovery after macular hole (MH) closure with pars plana vitrectomy (PPV) using adaptive optics scanning light ophthalmoscopy and spectral domain optical coherence tomography., Methods: A pilot imaging study of four eyes from four subjects undergoing PPV for MH was conducted. Imaging with spectral domain optical coherence tomography and adaptive optics scanning light ophthalmoscopy was performed at varying time points after PPV., Results: Despite successful MH closure, disruption of the foveal inner segment ellipsoid zone was seen in all patients when imaged at a mean of 117 days after PPV. Disruption of the photoreceptor mosaic was seen using adaptive optics scanning light ophthalmoscopy at locations corresponding to regions of ellipsoid zone disruption on spectral domain optical coherence tomography. Cone density immediately surrounding these disruptions was normal, except for one patient. In 2 patients who were imaged serially up to 516 days after PPV, recovery of cone cells within regions of mosaic disruption could be detected over time., Conclusion: Photoreceptor disruption exists even after apparent MH closure. Remodeling of the foveal cone mosaic continues for many months after surgery, perhaps accounting for the delayed postoperative improvements of visual acuity in some patients. Spectral domain optical coherence tomography and adaptive optics scanning light ophthalmoscopy are useful tools for monitoring photoreceptor recovery after surgical closure of MH.

Purpose: To evaluate outer retinal structural abnormalities in patients with visual deficits after closed-globe blunt ocular trauma., Methods: Nine subjects with visual complaints after closed-globe blunt ocular trauma were examined between 1 month after trauma and 6 years after trauma. Spectral domain optical coherence tomography was used to assess the outer retinal architecture, whereas adaptive optics scanning light ophthalmoscopy was used to analyze the photoreceptor mosaic integrity., Results: Visual deficits ranged from central scotomas to decreased visual acuity. Spectral domain optical coherence tomography defects included focal foveal photoreceptor lesions, variable attenuation of the interdigitation zone, and mottling of the outer segment band, with one subject having normal outer retinal structure. Adaptive optics scanning light ophthalmoscopy revealed disruption of the photoreceptor mosaic in all subjects, variably manifesting as foveal focal discontinuities, perifoveal hyporeflective cones, and paracentral regions of selective cone loss., Conclusion: We observe persistent outer retinal disruption in subjects with visual complaints after closed-globe blunt ocular trauma, albeit to a variable degree. Adaptive optics scanning light ophthalmoscopy imaging allows the assessment of photoreceptor structure at a level of detail not resolvable using spectral domain optical coherence tomography or other current clinical imaging tools. Multimodal imaging seems to be useful in revealing the cause of visual complaints in patients after closed-globe blunt ocular trauma. Future studies are needed to better understand how photoreceptor structure changes longitudinally in response to various traumas.

Purpose: We surveyed inner retinal microscopic features in retinal and neurologic disease using a reflectance confocal adaptive optics scanning light ophthalmoscope (AOSLO)., Methods: Inner retinal images from 101 subjects affected by one of 38 retinal or neurologic conditions and 11 subjects with no known eye disease were examined for the presence of hyper-reflective features other than vasculature, retinal nerve fiber layer, and foveal pit reflex. The hyper-reflective features in the AOSLO images were grouped based on size, location, and subjective texture. Clinical imaging, including optical coherence tomography (OCT), scanning laser ophthalmoscopy, and fundus photography was analyzed for comparison., Results: Seven categories of hyper-reflective inner retinal structures were identified, namely punctate reflectivity, nummular (disc-shaped) reflectivity, granular membrane, waxy membrane, vessel-associated membrane, microcysts, and striate reflectivity. Punctate and nummular reflectivity also was found commonly in normal volunteers, but the features in the remaining five categories were found only in subjects with retinal or neurologic disease. Some of the features were found to change substantially between follow up imaging months apart., Conclusions: Confocal reflectance AOSLO imaging revealed a diverse spectrum of normal and pathologic hyper-reflective inner and epiretinal features, some of which were previously unreported. Notably, these features were not disease-specific, suggesting that they might correspond to common mechanisms of degeneration or repair in pathologic states. Although prospective studies with larger and better characterized populations, along with imaging of more extensive retinal areas are needed, the hyper-reflective structures reported here could be used as disease biomarkers, provided their specificity is studied further., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)

Purpose: To evaluate retinal structural and functional abnormalities in a patient with acute macular neuroretinopathy., Methods: An adaptive optics scanning light ophthalmoscope was used to image the photoreceptor mosaic and assess rod and cone structure. Spectral-domain optical coherence tomography was used to examine retinal lamination. Microperimetry was used to assess function across the macula., Results: Microperimetry showed reduced function of localized areas within retinal lesions corresponding to subjective scotomas. Spectral-domain optical coherence tomography imaging revealed attenuation of two outer retinal bands typically thought to reflect photoreceptor structure. Adaptive optics scanning light ophthalmoscope images of the photoreceptor mosaic revealed a heterogeneous presentation within these lesions. There were areas containing non-waveguiding cones and other areas of decreased cone density where the remaining rods had expanded to fill in the vacant space. Within these lesions, cone densities were shown to be significantly lower than eccentricity-matched areas of normal retina, as well as accepted histologic measurements. A 6-month follow-up revealed no change in rod or cone structure., Conclusion: Imaging of acute macular neuroretinopathy using an adaptive optics scanning light ophthalmoscope shows a preferential disruption of cone photoreceptor structure within the region of decreased retinal sensitivity (as measured by microperimetry). Adaptive optics-based imaging tools provide a noninvasive way to assess photoreceptor structure at a level of detail that is not resolved by use of conventional spectral-domain optical coherence tomography or other clinical measures.

Objective: To compare visual outcomes in phakic and pseudophakic eyes treated with monthly intravitreal ranibizumab for exudative age-related macular degeneration (AMD)., Design: Meta-analysis of individual patient data from 2 phase 3 clinical trials of intravitreal ranibizumab in neovascular AMD (Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in Age-Related Macular Degeneration [ANCHOR], ClinicalTrials.gov number, NCT00061594; and Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular Age-Related Macular Degeneration [MARINA], ClinicalTrials.gov number NCT00056836)., Participants and Controls: A total of 1137 patients from 2 phase 3 clinical trials., Methods: Phakic and pseudophakic eyes were treated with monthly intravitreal ranibizumab (0.3 mg or 0.5 mg), sham injections plus verteporfin photodynamic therapy (ANCHOR), or sham injections alone (MARINA)., Main Outcome Measures: Mean change from baseline in Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) and the proportion of patients gaining or losing 15 or more ETDRS letters., Results: After adjusting for baseline covariates, no differences were seen in mean change in VA for phakic versus pseudophakic eyes. Pseudophakic eyes were more likely to lose 15 or more letters of vision than phakic eyes at 12 months, but not at 24 months., Conclusions: Overall, in this analysis, lens status did not demonstrate an independent influence on mean VA for eyes treated with monthly ranibizumab. It is possible that phakic eyes may be less prone to severe vision loss., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the prevalence of venous collaterals after branch and central retinal vein occlusion, assess the association of venous collaterals with other clinical features (including visual acuity), and determine if treatment with intravitreal corticosteroids influences the development of new venous collaterals., Methods: Review of data from two multicenter randomized clinical trials in the Standard of Care versus COrticosteroid for REtinal Vein Occlusion (SCORE) Study., Results: Statistically significant associations of venous collaterals and visual acuity at baseline or at follow-up were not found. Treatment with intravitreal triamcinolone acetonide did not appear to influence the development of venous collaterals., Conclusion: In contrast to some previous reports, development of venous collaterals did not demonstrate an independent association with visual acuity in eyes with branch retinal vein occlusion or central retinal vein occlusion in the SCORE Study. Intravitreal steroid effects do not appear to influence the development of venous collaterals.

Purpose: We present a case series of four patients with unilateral, nonprogressive, yellow or white choroidal lesions of unknown etiology., Methods: Four healthy patients were referred to an academic medical retina practice for unusual fundus findings in one eye only. Both eyes of all four patients underwent clinical examination and retinal imaging, including fluorescein angiography, indocyanine green imaging, and optical coherence tomography. The outcome of this series was based on the clinical course of these patients and the features of the retinal images., Results: The differential diagnosis based on the clinical appearances for these unknown cases includes birdshot chorioretinopathy, lymphoma or reactive lymphoid hyperplasia, metastases, orbital and intraocular pseudotumor, and bacterial or fungal infection. Extensive workups for these clinical entities including HLA-A29, angiotensin-converting enzyme level and computed tomography of the chest, liver function testing, magnetic resonance imaging of the brain, and orbital ultrasound have remained negative., Conclusion: Clinical and imaging characteristics for the four patients include absence of intraocular inflammation, late staining of lesions on fluorescein angiography, and hypofluorescence of lesions on indocyanine green. Lesions were not visible in the retina or retinal pigment epithelium using time domain optical coherence tomography. However, enhanced depth imaging spectral-domain optical coherence tomography imaging available for one patient suggests that these lesions are localized to the choroid; further interpretation of this advanced imaging technique will likely prove useful in the future. The patients' clinical course has remained nonprogressive with no changes over a prolonged period of observation. These cases could represent atypical manifestations of known retinal disease diagnoses or variations of a new chorioretinal disease process.

Purpose: To investigate whether the use of the best of multiple measures of visual acuity as an endpoint introduces bias into study results., Methods: Mathematical models and Monte Carlo simulations were used. A model was designed in which a hypothetical intervention did not influence the visual acuity. The best of one or more postintervention measures was used as the outcome variable and was compared to the baseline measure. Random test-retest variability was included in the model., Results: When the better of two postintervention measures was used as the outcome variable with a sample size of 25, the model falsely rejected the null hypothesis 55% of the time. When the best of three measures was used, the false-positive rate increased to 90%. The probability of falsely rejecting the null hypothesis increased with increasing sample size, also increasing the number of measures used to select the outcome variable., Conclusions: Using the best of multiple measures as an outcome variable introduces a systematic bias resulting in false conclusions of improvement in that variable. The use of best of multiple measures of visual acuity as an outcome variable should be avoided.

Purpose: The purpose of this study was to evaluate the correlation between best-corrected visual acuity (BCVA) and macular thickness in patients with persistent macular edema treated with a dexamethasone intravitreal drug delivery system (dexamethasone DDS)., Methods: In a randomized, multicenter, controlled, parallel-group, dose-ranging study, patients with macular edema lasting at least 90 days despite treatment were randomized to observation or treatment with 350- or 700-microg dexamethasone DDS. Macular thickness was assessed in 80 patients using optical coherence tomography. Best-corrected visual acuity was measured using Early Treatment Diabetic Retinopathy Study methodology., Results: At baseline, macular thickness was significantly inversely correlated with BCVA (r = -0.406, P < 0.001). Patients treated with 350- or 700-microg dexamethasone DDS showed a significant decrease in macular thickness from baseline to Day 90 (P = 0.002). In the 700-microg dexamethasone DDS treatment group, there was a modest inverse correlation between changes in macular thickness from baseline to Day 90 and improvement in BCVA (r = -0.530, P = 0.009). In the 350-microg dexamethasone DDS treatment group, the correlation was weaker and not statistically significant (r = -0.206, P = 0.304)., Conclusion: The correlation between baseline BCVA and macular thickness in patients with persistent macular edema was modest. Improvement in BCVA after treatment with 700-microg dexamethasone DDS was consistent with changes in macular thickness measured using optical coherence tomography.

Purpose: To describe the evolution of a giant macular hole in a patient with Alport syndrome and review the literature., Methods: An observational case report is presented with serial clinical examination, visual acuity, fundus photographs, and ocular coherence tomography performed., Results: A man with Alport syndrome and a giant macular hole in one eye developed multiple, small lamellar macular holes which coalesced into a giant full thickness macular hole in the contralateral eye., Conclusions: Giant macular holes may occur in Alport syndrome. The mechanism and clinical progression appear to differ from that of idiopathic macular holes and, is likely related to an abnormality in Type IV collagen in basement membrane of retinal Muller cells. Anomalous vitreoretinal adhesion may also play a role. Previous cases of giant macular holes in the literature may not have been properly associated with Alport syndrome.

Purpose: To evaluate anti-VEGF and photodynamic therapy (PDT) for juxtafoveal and extrafoveal choroidal neovascularization (CNV) due to age-related macular degeneration (ARMD), ocular histoplasmosis syndrome (OHS), and degenerative myopia., Methods: A total of 10 eyes with juxtafoveal or extrafoveal choroidal neovascularization underwent intravitreal anti-VEGF therapy combined with verteporfin PDT (689 nm). Most treatments consisted of PDT every 12 weeks and either ranibizumab 0.5 mg every 4 weeks or bevacizumab 1.25 mg every 6 weeks, initiated concurrently. Retreatment criteria were persistent exudative signs on optical coherence tomography or fluorescein angiography., Results: Presenting visual acuity (VA) ranged from 20/20 to 20/60 (mean log MAR+/-SD, 0.338+/-0.16 (20/44 equivalent)). After a mean follow-up of 17.5 months, it ranged from 20/15 to 20/40 (mean log MAR+/-SD, 0.150+/-0.14 (20/28 equivalent); P=0.027, paired t-test). Six eyes improved by > or = 2 lines and four remained within 2 lines of initial VA. Non-ARMD eyes required much fewer treatments than ARMD eyes. All five non-ARMD eyes and three of five ARMD eyes showed no CNV activity at least 5 months after last treatment., Conclusions: Anti-VEGF therapy and PDT can preserve good visual function and may be suited to some cases of nonfoveal CNV. ARMD eyes require longer courses of treatment than non-ARMD eyes.

Spectral domain optical coherence tomography (SD-OCT) images from an infant victim of shaken baby syndrome who presented with vitreous hemorrhage in the left eye and bilateral, large hemorrhages over both maculae. Both RetCam and SD-OCT images were obtained, demonstrating the position of the blood beneath the internal limiting membrane of the right macula. Image registration software was used to register the photographic images with the surface projection images obtained by the SD-OCT. In the left eye, the vitreous hemorrhage was removed with vitrectomy, and the retinoschisis cavity incised to allow drainage., (Copyright 2010, SLACK Incorporated.)

Objective: To evaluate the safety and efficacy of a dexamethasone intravitreous drug delivery system (DDS) in eyes with diabetic macular edema (DME)., Methods: Patients with persistent macular edema (> or = 90 days' duration) were randomized to treatment with 700 microg or 350 microg of dexamethasone DDS or observation. One eye from each patient was designated as the study eye. The analysis is of the eyes in this study with DME (n = 171)., Main Outcome Measures: The primary outcome measure was the proportion of eyes that achieved an improvement in best-corrected visual acuity (BCVA) of 10 letters or more from baseline at day 90. Other outcome measures included fluorescein leakage, central retinal thickness, and safety parameters., Results: At day 90, a BCVA improvement of 10 letters or more was seen in more eyes in the 700-microg group (33.3%) and 350-microg group (21.1%) than the observation group (12.3%; P = .007 vs 700-microg group). At day 180, a BCVA improvement of 10 letters or more was seen in 30% of eyes in the 700-microg group, 19% in the 350-microg group, and 23% in the observation group (P > or = .4 for treated vs observed eyes). There were also significantly greater improvements in central retinal thickness and fluorescein leakage in treated eyes than observed eyes (P = .03; day 90). Dexamethasone DDS was well tolerated., Conclusions: In eyes with persistent DME, treatment with 700 microg of intravitreal dexamethasone DDS is well tolerated and produces significant improvements in BCVA, central retinal thickness, and fluorescein leakage compared with observation (statistically significant at day 90)., Application to Clinical Practice: Dexamethasone DDS, 700 microg, may have potential as a treatment for persistent DME., Trial Registration: clinicaltrials.gov Identifier: NCT00035906.

Purpose: To evaluate the effects of a dexamethasone intravitreous drug delivery system (dexamethasone DDS) in patients with persistent macular edema (ME) resulting from uveitis or Irvine-Gass syndrome., Design: Randomized, prospective, single-masked, controlled trial., Methods: Three hundred and fifteen patients with persistent (>or= 90 days) ME were randomized in a multicenter study to surgical placement of 350 or 700 microg dexamethasone DDS or observation. This study evaluated the subset of patients with uveitis or Irvine-Gass syndrome (n = 41). The primary outcome measure was the proportion of patients achieving a 10-letter or more improvement in best-corrected visual acuity (BCVA) at day 90. Change in fluorescein angiographic leakage and safety also were evaluated., Results: At day 90, a 10-letter or more BCVA improvement was seen in 41.7% (5/12) of patients in the 350-microg group, in 53.8% (7/13) of patients in the 700-microg group, and in 14.3% (2/14) of patients in the observation group (P = .029 vs the 700-microg group). Improvement in visual acuity persisted to day 180. A 15-letter or more improvement was achieved in 53.8% (7/13) of 700-microg patients vs 7.1% (1/14) of observed patients (P = .008). There were significantly greater reductions in fluorescein leakage in treated patients than in observed patients. Dexamethasone DDS was well tolerated. Throughout the study, an increase in intraocular pressure of 10 mm Hg or more was seen in 5 of 13 patients in the 700-microg group, in 1 of 12 patients in the 350-microg group, and in no patients in the observation group. There were no reports of endophthalmitis., Conclusions: In patients with persistent ME resulting from uveitis or Irvine-Gass syndrome, 700-microg dexamethasone DDS was well tolerated and produced statistically significant improvements in visual acuity and fluorescein leakage.

Purpose: Evaluation of safety and performance of an applicator-inserted dexamethasone drug delivery system., Methods: Patients with clinically observable macular edema were randomized to receive 700 microg dexamethasone drug delivery system via a pars plana incisional placement (n = 10) or a 22-gauge applicator insertion (n = 20). Outcome measures included assessment of procedure duration, the postinsertion wound, adverse events, intraocular pressure, and best-corrected visual acuity at baseline and days 1, 7, 14, 30, 60, 90, and 180., Results: Both procedures were well tolerated and none of the patients in the applicator group required sutures to close the insertion wound. The overall incidence of ocular adverse events was less in the applicator group (13/19; 68.4%) than the incisional group (9/10; 90%), although the difference was not statistically significant in this pilot study. Vitreous hemorrhage occurred in two patients in the incisional group and none in the applicator group. Increases in intraocular pressure were less frequent in the applicator group (3/19; 15.8%) than the incisional group (3/10; 30%). No cases of endophthalmitis or retinal detachment occurred in either group. The percentage of patients achieving improvement in visual acuity of >/=15-letters at Day 90 was similar in both groups; 40% (8/20) in the applicator group and 30% (3/10) in the incisional group., Conclusion: The dexamethasone drug delivery system applicator system performed well, allowing safe, effective, and sutureless intravitreal placement of 700 microg dexamethasone drug delivery system.

Objective: To evaluate a dexamethasone intravitreous drug delivery system (DDS) in patients with persistent (> or =90 days despite treatment) macular edema., Methods: This 6-month study randomized 315 patients with persistent macular edema with best-corrected visual acuity (BCVA) of 20/40 to 20/200 in the study eye to observation or a single treatment with dexamethasone DDS, 350 or 700 microg., Main Outcome Measures: Proportion of patients achieving a BCVA improvement of 10 or more letters or 15 or more letters, safety measures, change in fluorescein angiographic leakage, and central retinal thickness., Results: At day 90 (primary end point), an improvement in BCVA of 10 letters or more was achieved by a greater proportion of patients treated with dexamethasone DDS, 700 microg (35%) or 350 microg (24%), than observed patients (13%; P<.001 vs 700-microg group; P = .04 vs 350-microg group); an improvement in BCVA of 15 letters or more was achieved in 18% of patients treated with dexamethasone DDS, 700 microg, vs 6% of observed patients (P = .006). Results were similar in patients with diabetic retinopathy, vein occlusion, or uveitis or Irvine-Gass syndrome. During 3 months of observation, 11% of treated patients and 2% of observed patients had intraocular pressure increases of 10 mm Hg or higher., Conclusion: In persistent macular edema, a single dexamethasone DDS treatment produced statistically significant BCVA improvements 90 days after treatment and was well tolerated for 180 days. Application to Clinical Practice Dexamethasone DDS, 700 microg, may have potential as a treatment for persistent macular edema.

Purpose: To compare clinician and fundus photograph reading center assessments of the cytomegalovirus (CMV) retinitis area and change in the CMV retinitis area over time, and to investigate how these assessments correlate with the visual field (VF) of eyes with CMV retinitis., Design: Analysis of pooled data from 2 multicenter randomized clinical trials and 1 prospective multicenter epidemiologic study., Participants: Ninety-five eyes of 79 patients. At baseline, each eye had CMV retinitis restricted to zone 1 and/or zone 2 (approximately the photographable postequatorial retina), as assessed by the evaluating clinician., Methods: Comparison of CMV retinitis area, change in area over time as assessed by clinicians and a fundus photograph reading center, and correlation of these assessments with VF measurement., Main Outcome Measures: Cytomegalovirus retinitis area, change in CMV retinitis area over time, and VF score., Results: Baseline assessments of the mean retinitis area were, by clinicians, 12.8% of the total retinal area and, by the reading center, 6.3% of the total retinal area (P<0.001). There was a positive correlation between clinician and reading center assessments of retinitis area at baseline (rho = 0.77 and P<0.0001 by Pearson correlation and rho = 0.54 and P<0.001 by concordance). Both clinician and reading center size measures correlated negatively with VF (Spearman correlation rhos = -0.38 and -0.52, respectively; P<0.001 each). Mean changes in area over a 3-month interval were, by clinicians, +1.2% and, by the reading center, +1.1% (P = 0.68). Regression analysis showed a positive concordance (rho = 0.42, P<0.001). Change in VF over a 3-month interval did not correlate with change in retinitis area as assessed by clinicians or the reading center., Conclusions: Awareness of the similarities and differences between clinician and reading center assessments of CMV retinitis area should permit clinicians to apply research data to clinical practice more effectively. Clinician assessment of retinitis area correlates negatively with VF, a clinically meaningful visual outcome in patients with CMV retinitis.

Purpose: To describe the course of cytomegalovirus (CMV) retinitis in patients with AIDS in the era of highly active antiretroviral therapy (HAART)., Design: Multicenter, prospective, observational study., Participants: Two hundred seventy-one patients with AIDS and CMV retinitis., Methods: Follow-up every 3 months with medical history, ophthalmologic examination, laboratory testing, and fundus photographs. Photographs were evaluated for relapse of the retinitis (progression) by graders at a centralized reading center., Main Outcome Measure: Retinitis progression (movement of the border of a CMV lesion > or =750 microm over a > or =750-microm front or occurrence of a new lesion one-quarter disc area or more in size)., Results: The overall rate of retinitis progression was 0.10/person-year (PY); among those with CD4+ T-cell counts of <50/microl, it was 0.58/PY, compared to 0.02/PY among those with CD4+ T-cell counts of > or =200/microl (P<0.0001). In the multivariate analysis, significant risk factors for retinitis progression included a low CD4+ T-cell count, positive CMV load, longer time from AIDS diagnosis, and low Karnofsky score., Conclusions: Compared with the rate of retinitis progression (approximately 3.0/PY) reported in the pre-HAART era, the rate of retinitis progression was reduced among patients in the HAART era, even among those with low CD4+ T-cell counts, who might be expected to behave most like patients from the pre-HAART era. However, these events also occurred among patients with high CD4+ T-cell counts and presumed immune recovery. Continued ophthalmologic follow-up of patients with immune recovery is recommended to detect early retinitis progression.

Purpose: To describe the course of cytomegalovirus (CMV) retinitis in patients with AIDS in the era of highly active antiretroviral therapy (HAART)., Design: Multicenter, prospective, observational study., Participants: Two hundred seventy-one patients with AIDS and CMV retinitis., Methods: Follow-up every 3 months with medical history, ophthalmologic examination, laboratory testing, and fundus photographs., Main Outcome Measure: Second (contralateral) eye involvement among patients with unilateral disease and retinal detachment (RD)., Results: The overall rate of second eye involvement among patients with unilateral CMV retinitis was 0.07 per person-year (PY); among those with CD4+ T-cell counts of <50/microl it was 0.34/PY, compared with 0.02/PY among those with CD4+ T-cell counts of > or =200/microl (P<0.0001). Risk factors for contralateral eye involvement included low CD4+ T-cell count and detectable CMV load. The overall rate of RD was 0.06/PY; among those with CD4+ T-cell counts of <50/microl it was 0.30/PY, compared with 0.02/PY among those with CD4+ T-cell counts of > or =200/microl (P<0.0001). Risk factors for RD included a low CD4+ T-cell count and larger area of CMV retinitis., Conclusions: Compared with the rates reported in the pre-HAART era of second eye involvement (approximately 0.40/PY) and RD (approximately 0.50/PY), the rates of these events were reduced among patients in the HAART era. However, among patients with CD4+ T-cell counts of <50/microl, the rates were more similar to those from the pre-HAART era.

Purpose: To describe the presenting characteristics and management alternatives of posterior chamber intraocular lens (PC-IOL) dislocation secondary to dehiscence of the zonules supporting the capsular bag., Design: Observational case series., Methods: Multicenter retrospective analysis of the surgical treatment and predisposing factors associated with 25 eyes of 22 patients with dislocation of the PC-IOL encased within the capsular bag secondary to dehiscence of the zonules supporting the capsular bag., Results: The dislocated in-the-bag PC-IOL was replaced with an anterior chamber intraocular lens in 60% or repositioned/exchanged and scleral fixated in 40% of eyes. Associated conditions included pseudoexfoliation syndrome 44%, uveitis 16%, and trauma 16%. There was no identifiable cause in 24% of eyes., Conclusions: In-the-bag PC-IOL dislocations are an unusual, sometimes bilateral, late complication of cataract surgery that can be managed by exchange with an anterior chamber intraocular lens or by PC-IOL repositioning or replacement with scleral fixation. The most common associated condition was pseudoexfoliation.

Purpose: To describe the presenting features and surgical outcomes in a series of children with rhegmatogenous retinal detachments., Design: Retrospective, noncomparative, interventional case series., Participants: Thirty-nine eyes of 34 children 18 years of age or younger undergoing surgery for rhegmatogenous retinal detachment., Methods: Patients were identified by chart review at two affiliated tertiary care centers. Risk factors for retinal detachment were classified into four categories: (1). congenital or developmental structural ocular abnormalities, (2). trauma, (3). previous ophthalmologic surgery, and (4). preceding uveitis., Results: Median age was 10 years, and 79% of patients were boys. Nine patients (26%) had bilateral retinal detachment at presentation, or experienced a detachment in their second eye before their nineteenth birthday. Every eye had at least one risk factor for retinal detachment, and more than half had risk factors in two or more categories. Structural abnormalities were most common (56%). Fifty-one percent of eyes underwent previous surgery, 36% experienced trauma, and 15% had uveitis. Detachments tended to be complex. Median follow-up was 24 months. Retinal reattachment was achieved in 79% of eyes; however, visual recovery was modest. Median preoperative and postoperative visual acuities were counting fingers and 20/400, respectively. Predictors of a poor visual outcome were: unmeasurable or light perception-only preoperative vision (P = 0.0001), macula-off retinal detachment (P = 0.01), the need for vitrectomy surgery (P = 0.01), the presence of proliferative vitreoretinopathy grade C or worse (P = 0.02), and the use of silicone oil (P = 0.02)., Conclusions: Predisposing factors in pediatric retinal detachments, particularly congenital and developmental structural abnormalities, may be more common than previously reported. Modern vitreoretinal surgical techniques can help achieve retinal reattachment in most cases. Many factors contribute to the limited visual recovery in this patient population. Predictors of visual outcomes are similar to those observed in adults. Inability of the clinician to determine confidently the preoperative visual acuity is a newly identified predictor of poor visual outcomes.

Objective: To evaluate rates and causes of visual loss among patients with acquired immunodeficiency syndrome (AIDS) and cytomegalovirus (CMV) retinitis before widespread availability of highly active antiretroviral therapy (HAART)., Methods: Data from 681 patients with AIDS and newly diagnosed or relapsed CMV retinitis who enrolled in 3 clinical trials conducted by the Studies of Ocular Complications of AIDS (SOCA) Research Group (between 1990 and 1996) were combined to evaluate the rates and causes of visual loss. Visual acuity and visual field (Goldmann visual fields) losses were evaluated., Results: The rates of visual loss in eyes with CMV retinitis were substantial in all 3 clinical trials, ranging from 51.7 to 97.7 events per 100 eye-years for loss of visual acuity to worse than 20/40 and 18.9 to 49.1 events per 100 eye-years for loss of visual acuity to 20/200 or worse. The 2 major causes of visual loss were retinitis, involving either the macula or the optic nerve, and retinal detachment. After 1992, visual outcomes improved significantly. Antiretroviral therapy was associated with a 30% reduction in the risk of visual acuity loss (relative risk, 0.70; P =.02)., Conclusions: In the pre-HAART era, visual morbidity was substantial. However, there was a secular trend for improved outcomes. The principal causes of visual loss were CMV involvement of the posterior retina and retinal detachment.

Purpose: To evaluate whether cytomegalovirus resistant to ganciclovir, detected in either the blood or urine, correlates with adverse ocular outcomes., Design: Prospective cohort study., Methods: Patients with cytomegalovirus and AIDS were enrolled in a study of the occurrence and clinical correlates of resistant cytomegalovirus. Blood and urine cultures for cytomegalovirus were performed at the time of diagnosis of retinitis, 1 and 3 months after the initiation of therapy, and every 3 months thereafter. Patients were seen monthly, at which time fundus photographs were obtained and forwarded to the Fundus Photograph Reading Center for evaluation of retinitis progression (movement of a border of a cytomegalovirus lesion > or = 750 microm, or the occurrence of a new lesion > or = 0.25 disk area in size) and the amount of retinal area affected by cytomegalovirus retinitis. Visual acuity was measured using logarithmic visual acuity charts. Phenotypic resistance to ganciclovir was defined as an IC50 > 6.0 micromol/l, and genotypic resistance to ganciclovir was defined as the occurrence of a cytomegalovirus UL97 gene mutation known to confer ganciclovir resistance. Time-dependent analyses were performed and included viral resistance, highly active antiretroviral therapy, and treatment variables as predictors of clinical outcomes., Results: One hundred ninety-seven patients received ganciclovir therapy. Nineteen patients developed phenotypic resistance to ganciclovir, and 18 developed genotypic resistance. The detection of cytomegalovirus resistant to ganciclovir was associated with a 4.17- to 5.61-fold increase in the odds of retinitis progression (P values all < or = .0002), depending upon the definition of resistance and the culture sources analyzed. Resistance was associated with a greater increase in retinal area involved by cytomegalovirus by 3-month interval (1.10% vs 0.05% to 0.10%), which was significant for phenotypic resistance and for genotypic resistance in the blood or urine (P =.012 to.021). There was a suggestion that resistance was associated with a greater loss of visual acuity (P =.009 to.096). Highly active antiretroviral therapy was associated with an approximate 50% reduction in the odds of retinitis progression, and the ganciclovir implant was associated with an approximate 60% reduction., Conclusions: The detection of cytomegalovirus resistant to ganciclovir in either the blood or urine of a patient with cytomegalovirus retinitis is associated with an increased risk of adverse ocular outcomes.

Cytomegalovirus (CMV) resistance to ganciclovir occurs via mutations in the UL97 gene. CMV DNA, from vitreous and blood specimens and from culture isolates from 87 patients with acquired immunodeficiency syndrome and CMV retinitis who received a ganciclovir implant, was sequenced to identify the relationship between the UL97 DNA sequences in the eye and peripheral blood. There was 93.5% agreement between the UL97 gene sequences from paired vitreous specimens and blood specimens. Sequence analysis of vitreous specimens showed that 15% (13/87) of the patients had either a ganciclovir resistance-conferring mutation or a polymorphism in the CMV UL97 gene. Eleven of the 13 mutations or polymorphisms in the vitreous also were identified in blood. Although the number of mutations limits definitive interpretation, these data suggest that blood specimens may reflect the events occurring in the eyes of patients with CMV retinitis.

Purpose: To assess the accuracy and precision of methods in clinical use for intraocular drug injection., Design: Experimental laboratory investigation., Methods: A total of 800 injections were performed using 20 different 1-ml syringes at intended volumes of 0.10 ml and 0.05 ml. The volume of each injection was calculated from mass of water delivered onto an analytic balance., Results: The mean measured volume delivered was less than the intended volume for every syringe (P <.001 for each syringe at each volume). A total of 7% and 22% of injections differed by 20% or more from the intended volumes of 0.10 ml and 0.05 ml, respectively. Overdelivery of volume was uncommon., Conclusion: Clinically relevant materials and methods used for intraocular injection of drugs systematically underdelivered the intended volume.

Objective: To investigate the size and distribution of lesions in newly diagnosed cytomegalovirus retinitis (CMVR)., Design: Retrospective, observational case series., Participants: Fundus photographs of 252 newly diagnosed CMVR lesions in 173 eyes of 130 patients (123 male, 7 female)., Methods: Thirty-five millimeter (60 degrees ) color transparencies were digitized. A montage of the retina was assembled for each involved eye and was superimposed on a specially designed map of the postequatorial retina. Cytomegalovius retinitis lesions were delineated, and the size and location of each lesion was measured. The size of newly diagnosed CMVR lesions was computed in terms of percent postequatorial retinal surface area (PERSA), and the location of lesions was plotted on a polar coordinate system., Main Outcome Measures: Size and location of patches of newly diagnosed CMVR., Results: The median lesion size was 3% PERSA. Peripheral CMVR lesions were larger than posterior ones (P < 0.001). The mean number of lesions was 1.6 per eye. The total area of CMVR involvement ranged from 1% to 76% PERSA, with a median of 5% PERSA. There was no difference between left and right eyes in the distribution of lesion centers (P = 0.27). The concentric distribution of lesion centers appeared to be homogeneous, except for fewer centers in the most peripheral 14 degrees (P < 0.001), and a greater than expected number of lesion centers in the macula (central 11.6 degrees, P < 0.001). Eyes of patients with unilateral retinitis had 1.3 lesions per involved eye compared with eyes of patients with bilateral retinitis, which had 1.6 lesions per eye (P = 0.003)., Conclusions: Most newly diagnosed CMVR lesions were small. Peripheral lesions were larger than more posterior lesions. Variations from a homogeneous distribution of lesions were noted only at the extreme peripheral and central locations and are probably explained by ascertainment bias. The macula was not spared from new CMVR lesions in this patient population.

Purpose: Cytomegalovirus retinitis is the most common intraocular infection in patients with acquired immunodeficiency syndrome (AIDS). With prolonged suppressive anticytomegalovirus maintenance therapy, resistance occurs in over 25% of patients. We evaluated longitudinal changes in the cytomegalovirus genotype in patients with cytomegalovirus retinitis who developed ganciclovir resistance that was demonstrated in either the blood or urine., Methods: Patients with AIDS and previously untreated cytomegalovirus retinitis were followed prospectively for the occurrence of resistance while on treatment. Blood and urine specimens were obtained periodically for cytomegalovirus culture according to a predetermined schedule. Positive isolates were tested for phenotypic susceptibility and for mutations in the UL97 and UL54 genes., Results: A mutation conferring resistance to ganciclovir in either the UL97 or UL54 gene was detected in 18 patients. In general, patients with a genotypically resistant virus developed increasing phenotypic resistance over time. There was a suggestion that unless therapy was changed, UL97 mutations tended to persist. In seven of eight patients, the mutations identified in isolates from the blood and urine were identical. In selected patients, there was a suggestion that a mixed population of cytomegalovirus might be present. Progression of the retinitis in an involved eye (15 of 18), contralateral eye retinitis (10 of 11), and extraocular cytomegalovirus disease (5 of 18) occurred commonly among patients with resistant virus., Conclusion: Resistance-conferring mutations in the cytomegalovirus genome emerge and may persist when the selective pressure for resistance is maintained. Some patients appear to harbor complex subpopulations of virus with different mutations and different levels of phenotypic resistance. Changes in therapy may result in a shift in virus population and changes in the cytomegalovirus genotype identified.

Purpose: To present a case of choroidal neovascularization associated with sympathetic ophthalmia successfully treated with photocoagulation., Design: Interventional case report., Methods: A 41-year-old man with a history of penetrating injury right eye, as well as sympathetic ophthalmia left eye, developed a classic choroidal neovascular membrane that threatened the center of the fovea., Results: The patient was treated with argon laser photocoagulation. He has maintained stable visual acuity without evidence of recurrence of the membrane with 4 years' follow-up., Conclusion: Thermal laser should be considered as a treatment option in cases of choroidal neovascularization associated with sympathetic ophthalmia.

Cytomegalovirus (CMV) retinitis is among the most common opportunistic infections in patients with acquired immunodeficiency syndrome. In a prospective study of 210 patients with CMV retinitis, 26 were identified as having either a phenotypic or a genotypic ganciclovir-resistant isolate from either blood or urine cultures. For blood culture isolates with an IC(50) >6.0 microm for ganciclovir, the sensitivity and specificity for detecting a UL97 mutation were 95% and 98%, respectively, whereas for an IC(50) >8.0 microM they were 79% and 99%, respectively. Although there were trade-offs between the 2 thresholds for blood culture isolates, for urine culture isolates an IC(50) >8.0 microM appeared to be better at identifying genotypic resistance. UL97 mutations identified in both the blood and urine cultures of individual patients were identical in 87.5% of cases. High-level ganciclovir resistance (IC(50), >30 microM) typically, but not invariably, was associated with a mutation in both the UL97 and UL54 genes.

Purpose: To evaluate, describe, and categorize the clinical presentation, clinical course, histopathology, and response to therapy in patients without a history of penetrating ocular trauma who developed sympathetic ophthalmia following pars plana vitrectomy., Methods: The records of patients without a history of trauma who underwent pars plana vitrectomy and developed sympathetic ophthalmia were retrospectively reviewed. Cases were analyzed with respect to clinical presentation, fluorescein angiographic findings, anatomic and visual outcomes, histopathology, and response to therapy., Results: Eight eyes were identified. The median age at presentation was 55 years, with a range of 14 to 62 years. The time from vitrectomy to diagnosis of sympathetic ophthalmia ranged from 2 months to greater than 2 years, with a median of 7 months. Six of eight patients (75%) presented with anterior chamber reaction. All eight patients presented with a vitreous inflammatory response. The optic nerve was inflamed clinically or angiographically in four of eight cases (50%). Small yellow-white sub-retinal pigment epithelial deposits were present in four of eight cases (50%). Two eyes had lesions characterized as multifocal choroiditis. One eye had larger yellow placoid-like lesions. One eye presented with vitritis but no retinal lesions. Subretinal choroidal neovascularization was noted in the inciting eye of one patient. Vision improved in the sympathizing eye with immunosuppressive therapy in five of eight cases (62.5%)., Conclusions: Sympathetic ophthalmia can be seen following pars plana vitrectomy in patients without penetrating injuries or a history of trauma. Indeed, it may be seen after successful vitrectomy for retinal detachment. Diverse clinical presentations are possible, and persistent or atypical uveitis following vitrectomy should alert the surgeon to the development of sympathetic ophthalmia.