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

Purpose: To investigate late retinal findings and complications of eyes with a history of retinopathy of prematurity (ROP) that did not meet treatment criteria and did not receive treatment during infancy. Design: Retrospective, nonconsecutive, noncomparative, multicenter case series. Participants: Three hundred sixty-three eyes of 186 patients. Methods: Data were requested from multiple providers on premature patients with a history of ROP and no treatment during infancy who demonstrated late retinal findings or complications and included age, gender, gestational age and weight, zone and stage at infancy, visual acuity, current retina vascularization status, vitreous character, presence of peripheral retinal findings such as lattice retinal tears and detachments (RDs), retinoschisis, and fluorescein findings. Main Outcome Measures: Rate of RDs and factors conferring a higher risk of RDs. Results: The average age was 34.5 years (range, 7-76 years), average gestational age was 26.6 weeks (range, 23-34 weeks), and average birth weight was 875 g (range, 425-1590 g). Findings included lattice in 196 eyes (54.0%), atrophic holes in 126 eyes (34.7%), retinal tears in 111 eyes (30.6%), RDs in 140 eyes (38.6 %), tractional retinoschisis in 44 eyes (11.9%), and visible vitreous condensation ridge-like interface in 112 eyes (30.5%). Fluorescein angiography (FA) was performed in 113 eyes, of which 59 eyes (52.2%) showed leakage and 16 eyes (14.2%) showed neovascularization. Incomplete vascularization posterior to zone 3 was common (71.6% of eyes). Retinal detachments were more likely in patients with a gestational age of 29 weeks or less (P < 0.05) and in eyes with furthest vascularization to posterior zone 2 eyes compared with zone 3 eyes (P = 0.009). Conclusions: Eyes with ROP not meeting the treatment threshold during infancy showed various late retinal findings and complications, of which RDs were the most concerning. Complications were seen in all age groups, including patients born after the Early Treatment for Retinopathy of Prematurity Study. Contributing factors to RDs included atrophic holes within peripheral avascular retina, visible vitreous condensation ridge-like interface with residual traction, and premature vitreous syneresis. We recommend regular examinations and consideration of ultra-widefield FA examinations. Prospective studies are needed to explore the frequency of complications and benefit of prophylactic treatment and if eyes treated with anti-vascular endothelial growth factor therapy are at risk of similar findings and complications. (C) 2019 by the American Academy of Ophthalmology.

Importance Recent reports suggest that cilioretinal arteries (CRAs) confer protection against developing advanced age-related macular degeneration (AMD). Objective To further characterize the association between the presence of a CRA and incidence of geographic atrophy (GA) or choroidal neovascularization (CNV). Design This cohort study constituted an ad hoc secondary analysis of data from the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) and was performed at 44 clinical centers in the United States among participants in CATT with CNV in the study eye and without advanced AMD in the fellow eye at baseline. The presence of a CRA was determined by 2 graders, masked to clinical data, using color fundus photographs, red-free fundus photographs, and fluorescein angiography. The proportion with CRAs at baseline between the study eye with CNV and fellow eye without CNV was first compared. The association of a CRA with incidence of CNV or GA at 5 years among fellow eyes and with incidence of GA among study (treated) eyes was then assessed. In addition, the association of CRAs with the Age-Related Eye Disease Study severity scale among the fellow eyes at baseline was assessed. Data were collected from February 1, 2008, through April 30, 2015, and analyzed from July 1, 2018, through April 30, 2019. Exposures Presence of a CRA. Main Outcomes and Measures The association between the presence of a CRA and incidence of CNV or GA at 5 years of follow-up. Results A total of 350 patients (700 eyes) (230 [65.7% women; mean [SD] age, 77 [7.2] years) were included in the analysis. Cilioretinal arteries were present in 67 of 345 (19.4%) fellow eyes without baseline CNV and 73 of 349 (20.9%) study eyes with baseline CNV (P = .60). Cilioretinal arteries in fellow eyes were not associated with incidence of CNV at 5 years (125 of 278 [45.0%] among eyes without CRAs and 30 of 67 [44.8%] among eyes with CRAs; P = .99) or with incidence of GA at 5 years (110 of 278 [39.6%] among eyes without CRAs and 25 of 67 [37.3%] among eyes with CRAs; P = .89). Cilioretinal arteries in study eyes were not associated with incidence of GA at 5 years (105 of 276 [38.0%] study eyes without CRAs and 26 of 73 [35.6%] study eyes with CRAs; P = .72). Conclusions and Relevance The analysis did not find a protective association between CRAs and incidence of CNV or GA among CATT participants who had unilateral exudative AMD. Why these findings were different from those of previous publications is unclear but may be partially explained by the different techniques used to detect CRAs or by the baseline advanced disease in CATT participants. Trial Registration ClinicalTrials.gov identifier: NCT00593450.

Yang, Sam S.; Ferrone, Philip J.; Gonzales, Christine R.; Schwartz, Steven D.Editor(s): McDonald, H Richard Author Information

A healthy 24-year-old man who had an unremarkable medical history and was not taking any medications presented to our clinic with a 2-week history of difficulty in reading with his right eye. His left eye had been “weak” since adolescence for no obvious reason. Initial examination revealed visual acuity of 20/40 in the right eye and 20/50 in the left eye. Slit-lamp biomicroscopic examination of both eyes demonstrated normal anterior segments and no evidence of vitreous cells. Fundus examination of the right eye revealed a normal optic disk, a macular neurosensory elevation overlying a yellow deposit, and normal peripheral retina. The left fundus had a normal optic disk, retinal pigment epithelium changes in the macula with a shallow neurosensory elevation temporally, and normal peripheral retina. Fluorescein angiography demonstrated leaking areas temporal to the fovea in each eye (Fig. 1). A diagnosis of central serous chorioretinopathy (CSC) was suspected; no treatment was offered, and the patient was requested to return for follow-up after 1 month. The patient returned 1 month later after seeing another ophthalmologist who suspected the diagnosis of choroiditis and suggested systemic steroid treatment. Visual acuity was stable at 20/40 in the right eye and 20/50 in the left eye; fundus examination revealed that the neurosensory elevation in the right eye was more prominent and there seemed to be more of the yellow deposit underneath the sensory elevation. A systemic workup was performed with the following findings: normal results of chest roentgenography, complete blood cell count, and liver function tests; and negative results of testing for IgG and IgM to Toxoplasma, HIV testing, syphilis (VDRL and TPHA) test, and testing for antinuclear antibodies, anticardiolipin antibodies, and rheumatoid factor. Systemic steroid treatment was initiated. During the following 5 days, visual acuity deteriorated rapidly to 20/100 in the right eye and 20/120 in the left eye. Steroid treatment was discontinued. A fluorescein angiogram demonstrated new leaking areas in both eyes (Fig. 2). Because visual acuity decreased significantly and the patient was stressed, focal laser treatment was directly applied to the leaking spots in the right eye. Ten days later, visual acuity was even worse at 20/240 in the right eye and 20/200 in the left eye. Clinical examination revealed a larger neurosensory detachment with retinal folds extending from the fovea toward the temporal edge of the detachment in the right eye and a neurosensory detachment temporal to the fovea in the left eye. A fluorescein angiogram demonstrated new leaking points in both eyes (Fig. 3), and laser treatment was applied again in both eyes. Laser treatment was applied for a third time in both eyes 10 days later due to persistent leakage and no improvement in the clinical appearance (Fig. 4). Only after the third laser treatment did vision start to improve gradually in both eyes, reaching 20/30 in the right eye and 20/40 in the left eye after 6 weeks (Fig. 5).

Purpose To present a case of bilateral endogenous endophthalmitis as the primary manifestation of an aortic root abscess and endocarditis, both of which were undetected by transesophageal echocardiogram. Design Observational case report. Methods A 13-year-old male presented with bilateral endogenous endophthalmitis and previously undiagnosed ventricular septal defect, subaortic stenosis, and a mitral valve cleft. Results Cardiac evaluation, systemic evaluation, and transesophageal echocardiogram were negative for endocarditis, but endocarditis and aortic root abscess were discovered at time of cardiac surgery. The patient responded to systemic treatment for endocarditis and surgical management of his cardiac defect. Conclusion A cardiac source for endogenous endophthalmitis should be considered in the presence of clinical diagnosis of bacteremia, despite a negative transesophageal echocardiogram and systemic evaluation.

BACKGROUND:Tumors of the retina are often seen in association with systemic syndromes such as neurofibromatosis, tuberous sclerosis, and von Hippel-Lindau disease. These masses are either astrocytic hamartomas or capillary hemangiomas. Retinal tumors unassociated with other systemic disease have also been reported.METHODS:The ophthalmologic evaluation and clinical course of a 65-year-old woman who developed an epiretinal membrane followed by a vascularized retinal mass in the macular area are described.RESULTS:Appearance and rapid growth of the lesion were documented with fundus photography and fluorescein angiography. The lesion was treated with photocoagulation following growth that threatened the foveal region. Choroidal neovascularization subsequently developed toward the fovea, and visual acuity has remained poor. After 4 years of follow-up no local recurrence or systemic disease possibly related to the tumor has occurred.CONCLUSIONS:This is the first report of documented appearance and rapid growth of a retinal tumor that resembles a reactive astrocytic hyperplasia.

Objective Silicone oil frequently is used as a vitreous substitute after complex vitreoretinal procedures. The authors sought to study the effect of short- and long-term exposure to silicone oil on polymethyl methacrylate (PMMA, MC60BM; Alcon, Ft. Worth, TX), silicone (SI-30NB; AMO, Irvine, CA), and soft acrylic (MA60BM; Alcon) intraocular lenses (IOLs). Design An experimental animal study. Intervention Forty-one New Zealand white rabbits underwent lensectomy, vitrectomy, capsulotomy, and placement of one of the three types of IOLs into the ciliary sulcus. All lenses were weighed before implantation and 24 hours after explanation. In the short-term study, an fluid-air exchange was performed followed by the use of silicone oil (1000 centistokes) to coat the posterior lens surface. Immediately thereafter, an air-fluid exchange was performed and the remaining silicone on the posterior lens surface was aspirated or wiped or both for 1 minute using a soft-tipped extrusion cannula for 1 minute. In the long-term study, the posterior segment was filled with 1000 centistokes silicone oil after fluid-air exchange. Animals were observed by slit-lamp biomicroscopy and photographed at 1 week, 1 month, and 3 months after surgery. At 3 months, all animals underwent silicone-fluid exchange, an attempt to manually remove any remaining silicone oil, and lens explanation. Results In the short-term study, no silicone oil remained after manual wiping and/or aspiration in any of the four rabbits implanted with PMMA or acrylic IOLs. In the animals with silicone IOLs, a significant amount of silicone oil remained on the posterior lens surface of all lenses (P < 0.01 for silicone vs. acrylic and silicone vs. PMMA). No statistically significant difference was found when comparing the lens weights in each group before and after implantation. In the long-term study, aqueous droplet formation was found on the posterior lens surface of six of nine PMMA IOLs and ten of ten silicone IOLs at 3 months. No opacities were observed in the group with acrylic IOLs (P < 0.001 for acrylic vs. silicone, P = 0.0018 for acrylic vs. PMMA, and P = 0.047 for PMMA vs. silicone). Adherent silicone oil remained on two of nine PMMA IOLs and on none of ten acrylic IOLs. In contrast, a significant amount of silicone oil remained on the posterior lens surface of ten of ten silicone IOLs (P < 0.001 for silicone vs. acrylic and silicone vs. PMMA). Furthermore, there was a statistically significant increase in lens weights before and after implantation in the silicone IOL group but not in the PMMA or acrylic group (P < 0.01). Conclusions It is extremely difficult or impossible to remove remaining silicone oil from the posterior surface of a silicone IOL after short- or long-term exposure to silicone oil. This oil may interfere with the surgeon’s view of the retina and may diminish the patient’s visual acuity. In contrast, oil is readily removed from the posterior surface of an acrylic IOL. The authors therefore recommend the use of a soft acrylic or PMMA IOL over a silicone IOL when choosing a lens for implantation in patients who may require vitreoretinal procedures with silicone oil tamponade.

Several authors have reported significant exposure rates using the hydroxyapatite orbital implant in the treatment of the anophthalmic socket. Histologic studies by ourselves and others have suggested that lack of fibrovascular ingrowth into the implants may contribute to conjunctival breakdown and exposure. Recently, much attention has been given to angiogenic factors, such as rTGF-beta 2 and those found in plasma, in accelerating wound healing and fibrovascular ingrowth. This pilot study compares the rate of vascularization of hydroxyapatite orbital implants pretreated with plasma, rTGF-beta 2, and a saline/gentamicin solution with that in untreated controls in a population of New Zealand albino rabbits.Hydroxyapatite orbital spheres were implanted subcutaneously and in enucleated orbits. Untreated implants were used as a control. Implants pretreated with plasma, rTGF-beta 2, and a saline/gentamicin solution were removed and examined histologically at weekly intervals for the first 3 weeks after implantation.Histologic studies demonstrated that the rate of vascularization significantly increased between 2 and 3 weeks postoperatively in all study groups. Pretreating the implants with rTGF-beta 2 in phosphate buffered solution (PBS) or autogenous plasma did not significantly increase the rate of vascularization in comparison with controls at weeks 1 and 2. However, pretreating the implants with a saline/gentamicin solution or PBS alone was associated with an increased rate of vascularization at weeks 2 and 3. No statistically significant difference in vascularization was noted between the subcutaneous and orbital implants at any week.Hydroxyapatite implants pretreated with saline/gentamicin or phosphate buffered solutions underwent more rapid vascularization at weeks 2 and 3 in comparison with controls. Additionally, all groups were noted to have a more rapid rate of ingrowth between weeks 2 and 3 than between weeks 1 and 2. Plasma and rTGF-beta 2 (at the dose used) did not significantly alter the rate of vascularization of hydroxyapatite implants during the first 2 to 3 weeks. The significance of these findings is discussed.

We developed a reproducible model of traction retinal detachment (TRD) in the cat eye by creating a serous retinal detachment and then injecting 2.5 x 10(5) kitten dermal fibroblasts into the vitreous cavity at the site of a retinal wound. Serous detachments were produced by exposing an area of retina to focused light after intravenous injection of rose bengal (a photosensitizing dye). TRD developed rapidly within the first 2 weeks after fibroblast injection, accompanied by the formation of vitreoretinal strands and, to a lesser degree, epiretinal and/or subretinal proliferation. Histopathology demonstrated fibroblasts within the vitreous or along the posterior hyaloid face. Focal deposits of fibroblasts were occasionally found on the inner surface of the retina and/or in the subretinal space. Fibroblast proliferation was confirmed by uptake of radiolabeled thymidine. Deposition of collagen was noted at as early as 3 days after fibroblast injection. Neovascularization was not observed. Control eyes that did not receive fibroblasts showed resolution of serous detachment without retinal traction. In all eyes, retinal degeneration and thinning were seen in the area of previous photodynamic treatment. In this model of TRD, anteroposterior traction (due to vitreous strands) predominates, as is observed in experimental posterior penetrating ocular injury induced by intravitreal blood injection, which also results in vitreous strand formation. Our model, however, enables clinical assessment of TRD in the cat without the media opacification produced by vitreous blood.

A condition similar to proliferative vitreoretinopathy (PVR) in man can be produced by injecting 25000 homologous dermal fibroblasts into rabbit eyes following gas compression of the vitreous. Daunorubicin (15 nmol) was effective in preventing retinal detachment in this model when injected simultaneously with the fibroblasts or in two doses (10 nmol followed by 5 nmol 4 h later) on the 3rd day after fibroblast injection. A single dose of 15 nmol on the 3rd day was not effective in preventing retinal detachment. These results suggest that daunorubicin may be clinically useful in preventing PVR when given by injection both at the time of vitrectomy as well as later, when protein exudation and pigment clumps in the vitreous cavity herald the onset of PVR.