Multimodal Analysis of the Retinal Manifestations of Tuberous Sclerosis Complex: A Case Series.

BACKGROUND AND OBJECTIVE: We used a multi-modal imaging approach including fundus fluorescein angiography (FFA) to assess the retinal lesions in tuberous sclerosis complex (TSC) and evaluate their correlation with intracranial tuber burden on magnetic resonance imaging (MRI). PATIENTS AND METHODS: Participants with TSC underwent bilateral fundus photography, optical coherence tomography (OCT), infrared (IR) imaging, and FFA. Participants' most recent MRI brain scans were analyzed to determine intracranial tuber load. RESULTS: Nine participants were included. OCT identified all retinal astrocytic hamartoma (RAH) lesions, IR identified 75%, fundus photography identified 63%, and FFA detected just 57%. On FFA, 20% of flat-type hamartomas and all multi-nodular and transitional types were hyperfluorescent. There were significant positive correlations between the quantities of intracranial tubers and all TSC-retinal lesions (r = 0.8, P < 0.01) and all RAH lesions (r = 0.8, P = 0.01). CONCLUSIONS: A multimodal imaging-based approach with fundal photography, IR imaging, and OCT should be used to assess the retina in TSC as it may indicate the intracranial tuber burden. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Evaluation of Inflammation in the Peripheral Multiple Sclerosis Retina Using Ultra-Widefield Optical Coherence Tomography: A Pilot Study.

BACKGROUND AND OBJECTIVE: Reports of fundus fluorescein angiography (FFA) in active multiple sclerosis (MS) have shown peripheral perivenous sheathing. We sought to assess the feasibility of ultra-widefield (UWF) FFA and optical coherence tomography (OCT) in assessing the peripheral retina in MS. MATERIALS AND METHODS: Participants with MS and healthy controls underwent bilateral UWF fundus photography and FFA. Swept-source OCTs were captured centrally, peripherally, and to delineate any abnormalities visualized. RESULTS: We recruited five people with relapsing remitting MS, with a mean age of 36.9 (± 9.9), mean disease duration of 11 years (± 6.3), and a median expanded disability status score of 0.75 (0 to 2.5). In all MS participants, the disease was not active clinically or radiologically. Using UWF-FFA and OCT, we did not detect clear evidence of peripheral retinal abnormalities, which is consistent with the participants having inactive MS. CONCLUSION: A pilot study using UWF-FFA and peripheral OCT to examine the retina in MS suggests that it may be useful to perform a larger prospective longitudinal study to establish its potential as a monitor of disease activity. [Ophthalmic Surg Lasers Imaging Retina 2023;54:586-588.].

Dysregulated claudin-5 cycling in the inner retina causes retinal pigment epithelial cell atrophy.

Age-related macular degeneration (AMD) is the leading cause of central retinal vision loss worldwide, with an estimated 1 in 10 people over the age of 55 showing early signs of the condition. There are currently no forms of therapy available for the end stage of dry AMD, geographic atrophy (GA). Here, we show that the inner blood-retina barrier (iBRB) is highly dynamic and may play a contributory role in GA development. We have discovered that the gene CLDN5, which encodes claudin-5, a tight junction protein abundantly expressed at the iBRB, is regulated by BMAL1 and the circadian clock. Persistent suppression of claudin-5 expression in mice exposed to a cholesterol-enriched diet induced striking retinal pigment epithelium (RPE) cell atrophy, and persistent targeted suppression of claudin-5 in the macular region of nonhuman primates induced RPE cell atrophy. Moreover, fundus fluorescein angiography in human and nonhuman primate subjects showed increased retinal vascular permeability in the evening compared with the morning. These findings implicate an inner retina-derived component in the early pathophysiological changes observed in AMD, and we suggest that restoring the integrity of the iBRB may represent a novel therapeutic target for the prevention and treatment of GA secondary to dry AMD.

Recurrence of retinal pigment epithelial changes after macular translocation with 360 degrees peripheral retinectomy for geographic atrophy.

OBJECTIVE: To assess the prevalence of recurrence of macular geographic atrophy (GA) of the retinal pigment epithelium (RPE) after macular translocation with 360 degrees retinectomy (MT360) in one institution. METHODS: A retrospective review of all cases of GA that were treated with MT360 in 1 institution. Demographic and clinical data including the duration of preoperative visual loss, preoperative and postoperative visual acuity, and the prevalence of postoperative foveal RPE atrophy were recorded for these patients, and these data were compared with similar data from patients who underwent MT360 for neovascular age-related macular degeneration (AMD) as part of the prospective Duke Macular Translocation Study, Duke University Eye Center, Durham, NC. RESULTS: Four eyes in 4 patients with GA secondary to AMD underwent MT360 and were compared with 63 eyes in 63 patients who underwent MT360 for neovascular AMD as part of the Duke Macular Translocation Study. The mean duration of preoperative visual loss was higher in the GA group (11.3 months) than in the neovascular AMD group (1.7 months) (P = .08). The prevalence of postoperative foveal RPE atrophy was significantly higher in the GA group (n = 3; 75.0%) than in the neovascular AMD group (n = 5; 8.3%) (P<.01); in the GA group, this corresponded to recurrence of the GA lesions. In contrast, the postoperative RPE atrophy seen in the neovascular AMD group was due to postoperative mechanical forces such as laser therapy or RPE tearing. There was no significant difference in the mean preoperative or postoperative visual acuity in either group. CONCLUSIONS: Subfoveal RPE atrophy can reoccur following MT360 in eyes with nonneovascular AMD and GA; RPE atrophy similar to this has not been found in a large consecutive series of patients with neovascular AMD after MT360. Further research is needed to assess if the potential for visual recovery in eyes with end-stage nonneovascular AMD is outweighed by the possibility of postoperative recurrence of GA.

Vision-related quality of life in patients with bilateral severe age-related macular degeneration.

PURPOSE: To determine the quality of life (QOL) of patients with bilateral severe age-related macular degeneration (AMD) before macular translocation with 360 degrees peripheral retinectomy. DESIGN: Prospective, consecutive, noncomparative case series. METHODS: An observational study assessed vision-related and general health QOL using the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) and the Medical Outcomes Study 12-item short form (SF-12) surveys, respectively. Mean QOL scores were correlated with patient age, duration of vision loss, and visual function. Mean QOL scores in study patients were compared with mean QOL scores in groups of patients with low vision, patients with AMD of varying severity, and reference populations. MAIN OUTCOME MEASURES: National Eye Institute VFQ-25 and SF-12 QOL scores. RESULTS: Seventy patients with a mean age of 76.4 years were studied. Mean distance visual acuity (VA) was 62.4 (Early Treatment Diabetic Retinopathy Study letters), mean near VA was 0.81 (logarithm of the minimum angle of resolution), and mean reading speed was 74.9 words per minute. Important NEI VFQ-25 quality of vision subscales (general vision, difficulty with distance tasks, difficulty with near tasks) and vision-specific subscales (dependency, role difficulties, mental health, social function limitations) tended to correlate negatively with increasing patient age and duration of vision loss, but correlated positively with better VA and reading speed. The mean QOL scores for these important quality of vision and vision-specific subscales were significantly worse than or similar to mean scores in patients with low vision, and significantly worse than scores in patients with AMD of varying severity and a reference population. The mean SF-12 physical composite score in study patients was similar to that seen in patients with AMD of varying severity, but significantly higher than that in patients with low vision and a reference population. The SF-12 mental composite score in study patients was similar to those of all 3 comparison groups. CONCLUSIONS: Patients with bilateral severe AMD have vision-related QOL similar to that of patients with low vision but significantly worse than those of patients with AMD of varying severity and persons without eye disease. This inability to perform vision-related daily tasks is not related to general health problems.

Quality of life after macular translocation with 360 degrees peripheral retinectomy for age-related macular degeneration.

PURPOSE: To determine patients' quality of life (QOL) after macular translocation with 360 degrees peripheral retinectomy (MT360) for age-related macular degeneration. DESIGN: Prospective, interventional, consecutive, noncomparative case series. METHODS: A prospective study assessed QOL 1 year after MT360 and its relation to postoperative visual function. The 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) and the Medical Outcomes Study 12-item short form (SF-12) health survey were used to assess vision-related QOL and general health, respectively. Surveys were administered preoperatively and postoperatively. Postoperative NEI VFQ-25 QOL and SF-12 subscale scores for all patients were compared with the preoperative scores. Preoperative and postoperative distance and near visual acuities (VAs) and reading speed were assessed. Changes in NEI VFQ-25 QOL subscale scores were compared in patients with and without improved visual function. Postoperative NEI VFQ-25 QOL subscale scores in patients with distance VA of >or=69 Early Treatment Diabetic Retinopathy Study letters, near VA of >or=20/70, and reading speed of >or=90 words per minute were compared with subscale scores in patients with worse postoperative visual function. MAIN OUTCOME MEASURES: National Eye Institute VFQ-25 and SF-12 QOL scores and their association with distance VA, near VA, and reading speed. RESULTS: In total, 50 patients with a mean age of 76.9 years were studied. Postoperative mean NEI VFQ-25 QOL scores were higher than the preoperative mean scores, and this difference was significant for important vision-specific subscales. Patients with improved visual function had greater mean changes in NEI VFQ-25 QOL scores than those with no improvement. Patients with the outlined higher levels of visual function had greater mean NEI VFQ-25 QOL scores than those who had worse visual function. Preoperative and postoperative mean SF-12 QOL scores were similar. CONCLUSIONS: Macular translocation with 360 degrees peripheral retinectomy was associated with improvement in vision-related QOL. The amount of improvement was greatest in patients with postoperative improvement in visual function, and the best postoperative vision-related QOL was seen in patients with better postoperative visual function. This was not associated with a change in patients' general health.

Meta-analysis of plasma homocysteine, serum folate, serum vitamin B(12), and thermolabile MTHFR genotype as risk factors for retinal vascular occlusive disease.

PURPOSE: To assess the role of plasma total homocysteine (tHcy) levels, serum folate and vitamin B(12)levels, and homozygosity for the thermolabile methylenetetrahydrofolate reductase genotype (TT) as risk factors for retinal vascular occlusive disease. DESIGN: Meta-analysis of literature. METHODS: A MEDLINE search was performed to identify all published case-control studies of plasma tHcy levels, serum folate and vitamin B(12) levels, and TT genotype in persons with retinal vascular occlusive disease. Main outcome measures included calculation of plasma tHcy, serum folate, and serum vitamin B(12) standard differences and odds ratios (OR) of TT genotype between cases and controls. RESULTS: In total, 614 patients with all types of retinal vein occlusion had higher plasma tHcy levels than 762 control subjects (standard difference, 0.867; 95% confidence interval [CI] = 0.735, 0.999; P <.001). Plasma tHcy levels were also higher in 154 patients with retinal artery occlusion compared with 358 control subjects (standard difference 1.174; 95% CI = 0.947, 1.402; P <.001). Serum folates, but not vitamin B(12) levels, were lower in 287 patients with retinal vascular occlusion than in the same number of control subjects (standard difference, 0.508; 95% CI = 0.340, 0.675; P <.001; and -0.060; 95% CI = -0.024, 0.104; P =.474, respectively). Similar proportions of 690 patients with retinal vein occlusion and 2754 control subjects demonstrated the TT genotype (OR = 1.332; 95% CI = 0.995, 1.783; P =.054) as did 152 patients with retinal artery occlusions and 435 control subjects (OR = 1.716; 95% CI = 0.977, 3.014; P =.060). CONCLUSIONS: Retinal vascular occlusion is associated with elevated plasma tHcy levels and low serum folate levels, but not serum vitamin B(12) levels and TT genotype. Until a prospective multicenter trial is undertaken, plasma tHcy levels and serum folate levels should be determined in patients with retinal vascular occlusions, and dietary supplementation with low doses of folate and vitamin B(12) should be considered for affected persons.

Rapid and durable recovery of visual function in a patient with von hippel-lindau syndrome after systemic therapy with vascular endothelial growth factor receptor inhibitor su5416.

PURPOSE: To present a case of rapid and durable recovery of visual function in a patient with von Hippel-Lindau syndrome and optic nerve head hemangioblastoma after systemic treatment with the vascular endothelial growth factor (VEGF) receptor inhibitor SU5416. DESIGN: Interventional case report. METHODS: Visual function parameters, including visual acuity, automated visual field, and contrast sensitivity, were evaluated using standardized methods repeatedly over a 15-month period. Fundus photographs and fluorescein angiograms were also obtained. Central nervous system lesions were monitored by computed tomography (CT) and magnetic resonance imaging (MRI) scans. Treatment involved the systemic administration of the VEGF receptor inhibitor SU5416. MAIN OUTCOME MEASURES: Clinical presentation, visual acuity using Early Treatment Diabetic Retinopathy Study protocol, Humphrey automated perimetry, (Zeiss Humphrey Systems, Dublin, CA) Vistech contrast sensitivity (Vistech Consultants Inc., Dayton, OH) Farnsworth (Farnsworth-Munsell Color Services, New Windsor, NY) dichotomous panel D-15, retinal photography, fluorescein angiography, and CT and MRI scans. RESULTS: Within 4 weeks of therapy, visual acuity had improved from 20/32(-2) to 20/16(-1), the visual field had expanded from being circumferentially constricted to within 8 degrees of fixation to normal, and contrast sensitivity improved in all but the lowest spatial frequency (1.5 cycles/degree). No change was observed in lesion size by fundus photography. Improvement has been maintained over 18 months with intermittent SU5416 therapy. CONCLUSIONS: We report rapid, extensive, and durable recovery of visual function after systemic administration of the VEGF receptor inhibitor SU5416 to a patient with VHL syndrome and optic nerve head hemangioblastoma. These findings suggest that continued evaluation of VEGF inhibitors for ocular neovascular disorders is warranted.

Adverse reaction characterized by chest pain, shortness of breath, and syncope associated with verteporfin (visudyne).

PURPOSE: To report a serious adverse reaction associated with verteporfin infusion. DESIGN: Observational case report. METHODS: Case report of a single individual undergoing photodynamic therapy (PDT) with verteporfin. RESULTS: A 77-year-old man with long-standing asymptomatic atrial fibrillation, but no known coronary artery disease experienced severe chest and neck pain, shortness of breath, and syncope while undergoing a fourth photodynamic therapy (PDT) treatment with verteporfin. This infusion had been preceded by three prior infusions; the first two were uneventful, and the third was associated with milder, but similar symptoms. Evaluation demonstrated that the chest pain was noncardiac in origin. CONCLUSION: As verteporfin continues to be used around the world, physicians must be alert to the possibility of serious adverse side effects associated with its use.

Arteriovenous sheathotomy for branch retinal vein occlusion.

Branch vein occlusion is a significant cause of visual loss attributed to retinal vascular disease and is second only to diabetic retinopathy. BVO nearly always occurs at an AV crossing because of compression of the vein by the artery, resulting in hemodynamic abnormalities in the vein, including thrombus formation, reversal of flow toward the artery, and AV collateral formation. Relatively little information is available on the natural history of BVO; most of what exists is derived from clinical trials, including the BVOS. Current treatment options focus on treating sequelae of the occluded venous branch, such as macular edema, retinal neovascularization, vitreous hemorrhage, and traction retinal detachment. A novel therapeutic approach is decompression of the AV crossing, which has had promising initial results including restoration of vision and reversal of hemodynamic abnormalities. A prospective, controlled, clinical trial is being organized to determine the role of AV sheathotomy in the treatment of BVO.