AN ASSOCIATION BETWEEN STELLATE NONHEREDITARY IDIOPATHIC FOVEOMACULAR RETINOSCHISIS, PERIPHERAL RETINOSCHISIS, AND POSTERIOR HYALOID ATTACHMENT.

PURPOSE: Stellate nonhereditary idiopathic foveomacular retinoschisis is a disorder characterized by splitting of the retina at the macula, without a known underlying mechanical or inherited cause. This study investigates demographic, anatomical, and functional characteristics of subjects with stellate nonhereditary idiopathic foveomacular retinoschisis, to explore potential underlying mechanisms. METHODS: In this single-site, retrospective, and cross-sectional, observational study, data were collected from 28 eyes from 24 subjects with stellate nonhereditary idiopathic foveomacular retinoschisis. Descriptive statistics were reported, based on the observed anatomico-functional features. RESULTS: The visual acuity remained stable (median 20/20) in all subjects over a median follow-up of 17 months. All cases demonstrated foveomacular retinoschisis within Henle's fiber layer, at the junction of the outer plexiform and outer nuclear layers. This schisis cavity extended beyond the limits of the macular OCT temporally in all eyes. In most affected eyes, there were documented features of peripheral retinoschisis and broad attachment of the posterior hyaloid at the macula. Functional testing in a cross-sectional subset demonstrated normal retinal sensitivity centrally but an absolute scotoma peripherally. CONCLUSION: Stellate nonhereditary idiopathic foveomacular retinoschisis seems to be associated with peripheral retinoschisis and anomalous or incomplete posterior hyaloid detachment. Despite chronic manifestation, this does not significantly affect central visual function but can manifest with profound loss of peripheral visual function.

Transplantation of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in Macular Degeneration.

PURPOSE: Transplantation of human embryonic stem cell (hESC)-derived retinal pigment epithelial (RPE) cells offers the potential for benefit in macular degeneration. Previous trials have reported improved visual acuity (VA), but lacked detailed analysis of retinal structure and function in the treated area. DESIGN: Phase 1/2 open-label dose-escalation trial to evaluate safety and potential efficacy (clinicaltrials.gov identifier, NCT01469832). PARTICIPANTS: Twelve participants with advanced Stargardt disease (STGD1), the most common cause of macular degeneration in children and young adults. METHODS: Subretinal transplantation of up to 200 000 hESC-derived RPE cells with systemic immunosuppressive therapy for 13 weeks. MAIN OUTCOME MEASURES: The primary end points were the safety and tolerability of hESC-derived RPE cell administration. We also investigated evidence of the survival of transplanted cells and measured retinal structure and function using microperimetry and spectral-domain OCT. RESULTS: Focal areas of subretinal hyperpigmentation developed in all participants in a dose-dependent manner in the recipient retina and persisted after withdrawal of systemic immunosuppression. We found no evidence of uncontrolled proliferation or inflammatory responses. Borderline improvements in best-corrected VA in 4 participants either were unsustained or were matched by a similar improvement in the untreated contralateral eye. Microperimetry demonstrated no evidence of benefit at 12 months in the 12 participants. In one instance at the highest dose, localized retinal thinning and reduced sensitivity in the area of hyperpigmentation suggested the potential for harm. Participant-reported quality of life using the 25-item National Eye Institute Visual Function Questionnaire indicated no significant change. CONCLUSIONS: Subretinal hyperpigmentation is consistent with the survival of viable transplanted hESC-derived RPE cells, but may reflect released pigment in their absence. The findings demonstrate the value of detailed analysis of spatial correlation of retinal structure and function in determining with appropriate sensitivity the impact of cell transplantation and suggest that intervention in early stage of disease should be approached with caution. Given the slow rate of progressive degeneration at this advanced stage of disease, any protection against further deterioration may be evident only after a more extended period of observation.

Adjustable versus non-adjustable sutures for strabismus.

BACKGROUND: Strabismus, or squint, can be defined as a deviation from perfect ocular alignment and can be classified in many ways according to its aetiology and presentation. Treatment can be broadly divided into medical and surgical options, with a variety of surgical techniques being available, including the use of adjustable or non-adjustable sutures for the extraocular muscles. There exists an uncertainty as to which of these techniques produces a better surgical outcome, and an opinion that the adjustable suture technique may be of greater benefit in certain situations. OBJECTIVES: To determine if either an adjustable suture or non-adjustable suture technique is associated with a more accurate long-term ocular alignment and to identify specific situations in which it would be of benefit to use a particular method. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 5); Ovid MEDLINE; Ovid Embase; LILACS; the ISRCTN registry; ClinicalTrials.gov and the ICTRP. The date of the search was 13 June 2017. We contacted experts in the field for further information. SELECTION CRITERIA: We included only randomised controlled trials (RCTs) comparing adjustable to non-adjustable sutures for strabismus surgery. DATA COLLECTION AND ANALYSIS: We used standard procedures recommended by Cochrane. Two review authors independently screened search results and extracted data. We graded the certainty of the evidence using the GRADE approach. MAIN RESULTS: We identified one RCT comparing adjustable and non-adjustable sutures in primary horizontal strabismus surgeries in 60 children aged less than 12 years in Egypt. The study was not masked and we judged it at high risk of detection bias. Ocular alignment was defined as orthophoria or a horizontal tropia of 8 prism dioptres (PD) or less at near and far distances. At six months, there may be a small increased chance of ocular alignment with adjustable sutures compared with non-adjustable sutures clinically, however, the confidence intervals (CIs) were wide and were compatible with an increased chance of ocular alignment in the non-adjustable sutures group, so there was no statistical difference (risk ratio (RR) 1.18, 95% CI 0.91 to 1.53). We judged this to be low-certainty evidence, downgrading for imprecision and risk of bias. At six months, 730 per 1000 children in the non-adjustable sutures group had ocular alignment. The study authors reported that there were no complications during surgery. The trials did not assess patient satisfaction and resource use and costs. AUTHORS' CONCLUSIONS: We could reach no reliable conclusions regarding which technique (adjustable or non-adjustable sutures) produced a more accurate long-term ocular alignment following strabismus surgery or in which specific situations one technique is of greater benefit than the other, given the low-certainty and chance with just the one study. More high-quality RCTs are needed to obtain clinically valid results and to clarify these issues. Such trials should ideally 1. recruit participants with any type of strabismus or specify the subgroup of participants to be studied, for example, thyroid, paralytic, non-paralytic, paediatric; 2. randomise all consenting participants to have either adjustable or non-adjustable surgery prospectively; 3. have at least six months of follow-up data; and 4. include reoperation rates as an outcome measure.

Spectral sensitivity measurements reveal partial success in restoring missing rod function with gene therapy.

Restored rod visual function after gene therapy can be established unequivocally by demonstrating that, after dark adaptation, spectral sensitivity has the shape characteristic of rods and that this shape collapses to a cone-like shape before rods have recovered after an intense bleach. We used these tests to assess retinal function in eight young adults and children with early-onset severe retinal dystrophy from Phase II of a clinical gene-therapy trial for RPE65 deficiency that involved the subretinal delivery of a recombinant adeno-associated viral vector carrying RPE65. We found substantial improvements in rod sensitivity in two participants: dark-adapted spectral sensitivity was rod-like after treatment and was cone-like before rods had recovered after a bleach. After 40 min of dark adaptation, one participant showed up to 1,000-fold sensitivity improvements 4 months after treatment and the second up to 100-fold improvements 6 months after treatment. The dark-adapted spectral sensitivities of the other six participants remained cone-like and showed little improvement in sensitivity.

Long-term effect of gene therapy on Leber's congenital amaurosis.

BACKGROUND: Mutations in RPE65 cause Leber's congenital amaurosis, a progressive retinal degenerative disease that severely impairs sight in children. Gene therapy can result in modest improvements in night vision, but knowledge of its efficacy in humans is limited. METHODS: We performed a phase 1-2 open-label trial involving 12 participants to evaluate the safety and efficacy of gene therapy with a recombinant adeno-associated virus 2/2 (rAAV2/2) vector carrying the RPE65 complementary DNA, and measured visual function over the course of 3 years. Four participants were administered a lower dose of the vector, and 8 were administered a higher dose. In a parallel study in dogs, we investigated the relationship among vector dose, visual function, and electroretinography (ERG) findings. RESULTS: Improvements in retinal sensitivity were evident, to varying extents, in six participants for up to 3 years, peaking at 6 to 12 months after treatment and then declining. No associated improvement in retinal function was detected by means of ERG. Three participants had intraocular inflammation, and two had clinically significant deterioration of visual acuity. The reduction in central retinal thickness varied among participants. In dogs, RPE65 gene therapy with the same vector at lower doses improved vision-guided behavior, but only higher doses resulted in improvements in retinal function that were detectable with the use of ERG. CONCLUSIONS: Gene therapy with rAAV2/2 RPE65 vector improved retinal sensitivity, albeit modestly and temporarily. Comparison with the results obtained in the dog model indicates that there is a species difference in the amount of RPE65 required to drive the visual cycle and that the demand for RPE65 in affected persons was not met to the extent required for a durable, robust effect. (Funded by the National Institute for Health Research and others; ClinicalTrials.gov number, NCT00643747.).

Genotype-dependent variability in residual cone structure in achromatopsia: toward developing metrics for assessing cone health.

PURPOSE: Gene therapy trials for inherited photoreceptor disorders are planned. Anatomical metrics to select the best candidates and outcomes are needed. Adaptive optics (AO) imaging enables visualization of photoreceptor structure, although analytical tools are lacking. Here we present criteria to assess residual photoreceptor integrity in achromatopsia (ACHM). METHODS: Two AOSLOs, at the Medical College of Wisconsin and Moorfields Eye Hospital, were used to image the photoreceptor mosaic of 11 subjects with ACHM and 7 age-matched controls. Images were obtained, processed, and montaged using previously described methods. Cone density and reflectivity were quantified to assess residual cone photoreceptor structure. RESULTS: All subjects with ACHM had reduced numbers of cone photoreceptors, albeit to a variable degree. In addition, the relative cone reflectivity varied greatly. Interestingly, subjects with GNAT2-associated ACHM had the greatest number of residual cones and the reflectivity of those cones was significantly greater than that of the cones in the subjects with CNGA3/CNGB3-associated ACHM. CONCLUSIONS: We present cone reflectivity as a metric that can be used to characterize cone structure in ACHM. This method may be applicable to subjects with other cone disorders. In ACHM, we hypothesize that cone numerosity (and/or density) combined with cone reflectivity could be used to gauge the therapeutic potential. As gene replacement would not be expected to add cones, reflectivity could be a more powerful AO-metric for monitoring the cellular response to treatment and could provide a more immediate indicator of efficacy than behavioral measures, which may take longer to change.

Nature of the visual loss in observers with Leber's congenital amaurosis caused by specific mutations in RPE65.

PURPOSE: To characterize visual losses associated with genetic mutations in the RPE65 gene that cause defects in the RPE-specific isomerase, RPE65. RPE65 is an important component of the retinoid cycle that restores 11-cis-retinal after its photoisomerization to its all-trans form. The defects investigated here cause Leber's congenital amaurosis (LCA2), an autosomal, recessively-inherited, severe, congenital-onset rod-cone dystrophy. METHODS: Vision was assessed in nine patients and 10 normal controls by measuring: (1) long-wavelength sensitive (L-) cone temporal acuity (critical flicker fusion frequency or cff) as a function of target illuminance, and (2) L-cone temporal contrast sensitivity as a function of temporal frequency at a fixed-target illuminance. Measurements were made by modulating either a 650-nm light superimposed on a 480-nm background or the red phosphor of a color monitor on a background produced by the monitor's blue phosphor. RESULTS: RPE65-mutant observers have severely reduced cffs with shallower cff versus log illuminance functions that rise with a mean slope of 4.53 Hz per decade of illuminance compared with 8.69 Hz in normal controls. Consistent with the cff differences, RPE65-mutant observers show losses in temporal contrast sensitivity that increase rapidly with temporal frequency. CONCLUSIONS: All RPE65-mutant observers have consistent and substantial losses in temporal acuity and sensitivity compared with normal observers. The losses can be characterized by the addition of two sluggish filters within the mutant visual pathway, both filters with a time constant of 29.5 ms (i.e., low-pass filters with cut-off frequencies of 5.40 Hz).

A prospective longitudinal study of retinal structure and function in achromatopsia.

PURPOSE: To longitudinally characterize retinal structure and function in achromatopsia (ACHM) in preparation for clinical gene therapy trials. METHODS: Thirty-eight molecularly confirmed ACHM subjects underwent serial assessments, including spectral domain optical coherence tomography (SD-OCT), microperimetry, and fundus autofluorescence (FAF). Foveal structure on SD-OCT was graded and compared for evidence of progression, along with serial measurements of foveal total retinal thickness (FTRT) and outer nuclear layer (ONL) thickness. Fundus autofluorescence patterns were characterized and compared over time. RESULTS: Mean follow-up was 19.5 months (age range at baseline, 6-52 years). Only 2 (5%) of 37 subjects demonstrated change in serial foveal SD-OCT scans. There was no statistically significant change over time in FTRT (P = 0.83), ONL thickness (P = 0.27), hyporeflective zone diameter (P = 0.42), visual acuity (P = 0.89), contrast sensitivity (P = 0.22), mean retinal sensitivity (P = 0.84), and fixation stability (P = 0.58). Three distinct FAF patterns were observed (n = 30): central increased FAF (n = 4), normal FAF (n = 11), and well-demarcated reduced FAF (n = 15); with the latter group displaying a slow increase in the area of reduced FAF of 0.03 mm(2) over 19.3 months (P = 0.002). CONCLUSIONS: Previously published cross-sectional studies have described conflicting findings with respect to the age-dependency of progression. This study, which constitutes the largest and longest prospective longitudinal study of ACHM to date, suggests that although ACHM may be progressive, any such progression is slow and subtle in most patients, and does not correlate with age or genotype. We also describe the first serial assessment of FAF, which is highly variable between individuals, even of similar age and genotype.

Retinal structure and function in achromatopsia: implications for gene therapy.

PURPOSE: To characterize retinal structure and function in achromatopsia (ACHM) in preparation for clinical trials of gene therapy. DESIGN: Cross-sectional study. PARTICIPANTS: Forty subjects with ACHM. METHODS: All subjects underwent spectral domain optical coherence tomography (SD-OCT), microperimetry, and molecular genetic testing. Foveal structure on SD-OCT was graded into 5 distinct categories: (1) continuous inner segment ellipsoid (ISe), (2) ISe disruption, (3) ISe absence, (4) presence of a hyporeflective zone (HRZ), and (5) outer retinal atrophy including retinal pigment epithelial loss. Foveal and outer nuclear layer (ONL) thickness was measured and presence of hypoplasia determined. MAIN OUTCOME MEASURES: Photoreceptor appearance on SD-OCT imaging, foveal and ONL thickness, presence of foveal hypoplasia, retinal sensitivity and fixation stability, and association of these parameters with age and genotype. RESULTS: Forty subjects with a mean age of 24.9 years (range, 6-52 years) were included. Disease-causing variants were found in CNGA3 (n = 18), CNGB3 (n = 15), GNAT2 (n = 4), and PDE6C (n = 1). No variants were found in 2 individuals. In all, 22.5% of subjects had a continuous ISe layer at the fovea, 27.5% had ISe disruption, 20% had an absent ISe layer, 22.5% had an HRZ, and 7.5% had outer retinal atrophy. No significant differences in age (P = 0.77), mean retinal sensitivity (P = 0.21), or fixation stability (P = 0.34) across the 5 SD-OCT categories were evident. No correlation was found between age and foveal thickness (P = 0.84) or between age and foveal ONL thickness (P = 0.12). CONCLUSIONS: The lack of a clear association of disruption of retinal structure or function in ACHM with age suggests that the window of opportunity for intervention by gene therapy is wider in some individuals than previously indicated. Therefore, the potential benefit for a given subject is likely to be better predicted by specific measurement of photoreceptor structure rather than simply by age. The ability to directly assess cone photoreceptor preservation with SD-OCT and/or adaptive optics imaging is likely to prove invaluable in selecting subjects for future trials and measuring the trials' impact.

Adjustable versus non-adjustable sutures for strabismus.

BACKGROUND: Strabismus, or squint, can be defined as a deviation from perfect ocular alignment and can be classified in many ways according to its aetiology and presentation. Treatment can be broadly divided into medical and surgical options, with a variety of surgical techniques being available, including the use of adjustable or non-adjustable sutures for the extraocular muscles. There exists an uncertainty as to which of these techniques produces a better surgical outcome, and also an opinion that the adjustable suture technique may be of greater benefit in certain situations. OBJECTIVES: To examine whether adjustable or non-adjustable sutures are associated with a more accurate long-term ocular alignment following strabismus surgery and to identify any specific situations in which it would be of benefit to use a particular method. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to January 2013), EMBASE (January 1980 to January 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to January 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (http://clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 17 January 2013. We also contacted experts in the field for further information. SELECTION CRITERIA: We planned to include only randomised controlled trials (RCTs) comparing adjustable to non-adjustable sutures for strabismus surgery. DATA COLLECTION AND ANALYSIS: We did not find any studies that met the inclusion criteria for this review. MAIN RESULTS: We did not find any studies that met the inclusion criteria for this review, therefore none were included for analysis. Results of non-randomised studies that compared these techniques are reported. AUTHORS' CONCLUSIONS: No reliable conclusions could be reached regarding which technique (adjustable or non-adjustable sutures) produces a more accurate long-term ocular alignment following strabismus surgery or in which specific situations one technique is of greater benefit than the other. High quality RCTs are needed to obtain clinically valid results and to clarify these issues. Such trials should ideally a) recruit participants with any type of strabismus or specify the subgroup of participants to be studied, for example, thyroid, paralytic, non-paralytic, paediatric; b) randomise all consenting participants to have either adjustable or non-adjustable surgery prospectively; c) have at least six months of follow-up data; and d) include re-operation rates as a primary outcome measure.

Intravitreal low molecular weight heparin and 5-Fluorouracil for the prevention of proliferative vitreoretinopathy following retinal reattachment surgery.

BACKGROUND: Proliferative vitreoretinopathy (PVR) is a significant cause of failure in retinal reattachment surgery. Various pharmacological agents have shown potential benefit in reducing postoperative PVR risk. OBJECTIVES: This review aimed to compare the use of intravitreal low molecular weight heparin (LMWH) alone or with 5-Fluorouracil (5-FU) versus placebo, as an adjunct in the prevention of PVR following retinal reattachment surgery. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 9), MEDLINE (January 1950 to October 2012), EMBASE (January 1980 to October 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 15 October 2012. SELECTION CRITERIA: We only included randomised controlled trials (RCTs) that compared intravitreal LMWH alone or with 5-FU, versus placebo for the prevention of postoperative PVR in patients undergoing primary vitrectomy for rhegmatogenous retinal detachment repair. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. The review authors contacted study authors for additional information. MAIN RESULTS: We included two RCTs (with a total of 789 participants) comparing LMWH with 5-FU infusion and placebo. However, we did not perform a meta-analysis because of significant heterogeneity between these studies. One study found a significant beneficial effect of LMWH with 5-FU in reducing postoperative PVR compared to placebo (RR: 0.48, 95% confidence interval: 0.25 to 0.92), in 174 patients who were viewed at high-risk of developing postoperative PVR. The other study included 615 unselected cases of rhegmatogenous retinal detachment and could not show a difference between LMWH with 5-FU infusion and placebo in reducing PVR rates (RR:1.45, 95% confidence interval: 0.76 to 2.76). AUTHORS' CONCLUSIONS: Results from this review indicate that there is inconsistent evidence from two studies on patients at different risk of PVR on the effect of LMWH and 5-FU used during vitrectomy to prevent PVR. Future research should be conducted on high risk patients only, until a benefit is confirmed at least in this patient subgroup.

Retinal dystrophies and gene therapy.

Retinal dystrophies are inherited disorders of photoreceptor and retinal pigment epithelial function that may result in severe visual impairment. Advances in molecular genetics have helped identify many of the gene defects responsible, and progress in gene transfer technology has enabled therapeutic strategies to be developed and applied. The first human clinical trials of gene therapy for RPE65 associated retinal dystrophy have shown promising initial results and have helped prepare the way for further trials of gene therapy for inherited retinal disorders. The results of these trials will provide further insight into the safety and efficacy of gene therapy for a range of currently untreatable and debilitating eye disorders.

Intravitreal low molecular weight heparin and 5-Fluorouracil for the prevention of proliferative vitreoretinopathy following retinal reattachment surgery.

BACKGROUND: Proliferative vitreoretinopathy (PVR) is a significant cause of failure in retinal reattachment surgery. Various pharmacological agents have shown potential benefit in reducing postoperative PVR risk. OBJECTIVES: This review aimed to compare the use of intravitreal low molecular weight heparin (LMWH) alone or with 5-Fluorouracil (5-FU) versus placebo, as an adjunct in the prevention of PVR following retinal reattachment surgery. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2010, Issue 5), MEDLINE (January 1950 to May 2010), EMBASE (January 1980 to May 2010), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) and ClinicalTrials.gov (http://clinicaltrials.gov). There were no language or date restrictions in the search for trials. The electronic databases were last searched on 24 May 2010. SELECTION CRITERIA: We only included randomised controlled trials (RCTs) that compared intravitreal LMWH alone or with 5-FU, versus placebo for the prevention of postoperative PVR in patients undergoing primary vitrectomy for rhegmatogenous retinal detachment repair. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. The review authors contacted study authors for additional information. MAIN RESULTS: We included two RCTs (with a total of 789 participants) comparing LMWH with 5-FU infusion and placebo. However, we did not perform a meta-analysis because of significant heterogeneity between these studies. One study found a significant beneficial effect of LMWH with 5-FU in reducing postoperative PVR compared to placebo (RR: 0.48, 95% confidence interval: 0.25 to 0.92), in 174 patients who were viewed at high-risk of developing postoperative PVR. The other study included 615 unselected cases of rhegmatogenous retinal detachment and could not show a difference between LMWH with 5-FU infusion and placebo in reducing PVR rates (RR:1.45, 95% confidence interval: 0.76 to 2.76). AUTHORS' CONCLUSIONS: Results from this review indicate that there is inconsistent evidence from two studies on patients at different risk of PVR on the effect of LMWH and 5-FU used during vitrectomy to prevent PVR. Future research should be conducted on high risk patients only, until a benefit is confirmed at least in this patient subgroup.

Intravitreal triamcinolone for the treatment of ischemic macular edema associated with branch retinal vein occlusion.

PURPOSE: To evaluate the safety and efficacy of intravitreal triamcinolone acetonide (IVTA) for ischemic macular edema associated with branch retinal vein occlusion (BRVO) and foveal ischemia. DESIGN: Prospective interventional case series. METHODS: setting: Clinical practice. study population: Eighteen eyes of 18 patients with macular edema associated with BRVO and foveal ischemia. intervention: Four mg IVTA. main outcome measures: Visual acuity (VA), optical coherence tomography, macular thickness measurements, and treatment-related complications. RESULTS: The mean duration of BRVO before treatment was 14 months. All patients were followed for a minimum of nine months, and 12 patients completed 12 months follow-up. The mean logarithm of the minimum angle of resolution (logMAR) VA improved significantly from 0.81 +/- 0.36 at baseline to 0.65 +/- 0.30 at one month (P = .03) but did not vary significantly from baseline at three, six, nine, and 12 months. Macular thickness improved significantly in all eyes from a mean of 400 +/- 134 mum preinjection, to 228 +/- 58 mum at one month (P < .01) and 256 +/- 121 mum at three months (P < .01) but did not vary significantly from baseline at six, nine, and 12 months. Eight eyes developed posterior subcapsular cataract, intraocular pressure (IOP) exceeded 21 mm Hg in four eyes, and two eyes developed vitreomacular traction during follow-up. CONCLUSIONS: IVTA is effective in reducing ischemic macular edema associated with BRVO and foveal capillary nonperfusion. This reduction is often associated with a temporary improvement in VA. Raised IOP and development of posterior subcapsular cataract are disadvantages of this treatment.