Adaptive optics retinal imaging in patients with usher syndrome.

Purpose: To determine the structure of the cone photoreceptor mosaic in the macula in eyes with retinitis pigmentosa related to Usher syndrome using adaptive optics fundus (AO) imaging and to correlate these findings with those of the standard clinical diagnostics. Methods: Ten patients with a genetically confirmed retinitis pigmentosa in Usher syndrome due to biallelic variants in MYO7A or USH2A were enrolled in the study. All patients underwent a complete ophthalmological examination including best corrected visual acuity (BCVA), spectral-domain optical coherence tomography (SD-OCT) with fundus autofluorescence photography (FAF), full-field (ffERG) and multifocal electroretinography (mfERG) and Adaptive Optics Flood Illuminated Ophthalmoscopy (AO, rtx1™, Imagine Eyes, Orsay, France). The cone density was assessed centrally and at each 0.5 degree horizontally and vertically from 1-4 degree of eccentricity. Results: In the AO images, photoreceptor cell death was visualized as a disruption of the cone mosaic and low cone density. In the early stage of the disease, cones were still visible in the fovea, whereas outside the fovea a loss of cones was recognizable by blurry, dark patches. The blurry patches corresponded to the parafoveal hypofluorescent ring in the FAF images and the beginning loss of the IS/OS line and external limiting membrane in the SD-OCT images. FfERGs were non-recordable in 7 patients and reduced in 3. The mfERG was reduced in all patients and correlated significantly (p <0.001) with the cone density. The kinetic visual field area, measured with III4e and I4e, did not correlate with the cone density. Conclusion: The structure of the photoreceptors in Usher syndrome patients were detectable by AO fundus imaging. The approach of using high-resolution technique to assess the photoreceptor structure complements the established clinical examinations and allows a more sensitive monitoring of early stages of retinitis pigmentosa in Usher syndrome.

Defining reference values of arterioles in healthy individuals for studies with adaptive optics imaging.

Purpose: To investigate age-dependent wall to lumen ratio (WLR) reference values for healthy individuals in adaptive optics imaging (AO). WLR serves as an objective, dimensionless parameter for the evaluation of structural changes in vessels caused by conditions like arterial hypertension, diabetes or vascular stenosis. Methods: 50 right eyes of healthy individuals were examined by adaptive optics imaging. The central big arterioles and smaller arterial branches at least one disc diameter away from the optic disc, approximately above or below the macula were measured by the manufacturer's software. The wall-lumen-ratio (WLR), the wall cross-sectional area (WCSA) and lumen diameter (LD) were assessed. Subsequent data analysis was performed with a focus on variables including age, gender and blood pressure. Results: Normative values for WLR, WCSA and LD in 5 different age groups could be established. However, no significant differences between the age groups were found. Intra-subject comparisons revealed significantly higher WLRs on peripheral branches when compared to central arterioles. WLR showed in this normotensive cohort no relevant correlation with the systolic, diastolic and mean blood pressure. Gender and intraocular pressure had no influence on the vascular parameters. Conclusion: AO is capable of examining vascular alterations in arterioles at an almost microscopic level. Age did not seem to alter WLR, normotensive blood pressure parameters showed also no significant impact. AO-based vessel analysis may provide clinically useful biomarkers for cardiovascular health and should be tested in future studies.

Introducing a customized low-cost macular buckle.

PURPOSE: To demonstrate a novel surgical technique that is a low-cost alternative to commercial implants for macular buckling in high myopia. METHODS: A silicon encircling band serves as the anchor. A second silicon circling band is employed, with a 10mm silicon strip to widen the posterior scleral indentation. This band is inserted posteriorly the lateral and inferior rectus muscles and pushed behind the globe, orienting it in a superior-temporal to inferio-nasal position with the silicone strip directly under the macula. For better visualization, the placement of the macular buckle is done under the microscope. RESULTS: The placement of the macular buckle led to reattachment of the central retina in treated patients during long-term follow-up. This technique eliminates the need for detaching a rectus muscle. Visual acuity remained stable throughout the follow-up period. CONCLUSION: This customized macular buckle technique can improve the anatomical outcome in patients with central retinal detachment due to high myopia.

A morphometric analysis of the retinal arterioles with adaptive optics imaging in RPE65-associated retinal dystrophy after treatment with voretigene neparvovec.

PURPOSE: To investigate the changes in retinal arterial architecture after treatment with voretigene neparvovec in patients with retinal dystrophy caused by bi-allelic mutations in the RPE65 gene. METHODS: Sixteen eyes treated with voretigene neparvovec at the University Eye Clinic in Tuebingen, Germany, underwent adaptive optics ophthalmoscopy (AO) imaging at baseline and 2 weeks, 1, 3, 6 and 12 months after treatment. Follow-up was performed in six eyes of four patients. For each eye, five different positions at arterial vessels were selected and the wall-to-lumen ratio (WLR), the lumen diameter (LD) and the wall cross-sectional area (WCSA) were measured by the manufacturer's software over the observational period. RESULTS: Vast retinal atrophy dominated all gained AO images. WLR fluctuated in the observation period without statistically significant change. LD and WCSA changed significantly after 2 weeks from the baseline examination and returned to values similar to baseline thereafter. There were no signs of inflammation such as macrophages or perivascular accumulated fluid visible. CONCLUSION: AO imaging of the retinal vessels in RPE65-associated retinal dystrophies (IRD) is challenging. There was no change in the retinal arterial vasculature over the observation period of 12 months that would indicate inflammatory changes. Decrease of the LD and WCSA shortly after treatment might be caused by the perioperative prednisolone intake. AO of retinal vessels can be used as a diagnostic module to complement monitoring the disease and effects of genetic treatments if the acquisition is possible in selected cases.

The Role and Views of Ophthalmologists During the COVID-19 Pandemic.

PURPOSE: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic forced ophthalmologists to adjust their working conditions to ensure patient and staff safety, while still providing effective and timely treatment. This international survey among ophthalmologists was initiated to capture what actions ophthalmologists were taking and what their opinions were on the risks of infection in their workplace, the delay in treatment, the use of telemedicine and telephone for appointments, and the regional specifications and measures implemented by the respective authorities. METHODS: An open-source web tool was used to develop an online survey, to which ophthalmologists worldwide were invited via e-mail using international mailing lists (Media Mice, Singapore; Texere Publishing Inc, USA; CGO Gerling) and incentivized using a lottery. The physicians provided their level of agreement relating to the offered statements and gave free answers to the questions regarding the actions taken (conducted November 5th 2020 to December 20th 2020). RESULTS: After 91,000 invitations, responses were collected from 1122 ophthalmologists. Despite the use of large international mailing lists, mainly doctors from Europe participated. Half of the participants expressed great concern about possible SARS-CoV-2 infection in their patients. A significant number of younger ophthalmologists (≤50 years: 76.9%, n = 313; >50 years: 69.6%, n = 181) feared the delays that COVID-19 could cause to treatment. Reductions in patient numbers were broadly observed, with more ophthalmologists of younger age reporting greater declines. Nearly all ophthalmologists indicated that they provided disinfectant and the majority also used masks and questionnaires for screening. For 60.3% (n = 412) of ophthalmologists, telephone calls reduced the risk of 'no-shows'; 71.6% (n = 497) disagreed that telemedical evaluation is possible without slit lamp findings and fundus photos; and 57.0% of participants felt content with the governmental measures during the COVID-19 pandemic. CONCLUSION: The COVID-19 pandemic has significantly influenced the work of ophthalmologists. Based on the limited response rate, certain statements were only possible to evaluate for the European Union: with a noticeable reduction in patient numbers, delay in treatment was a major worry. Measures to protect and reassure patients should be undertaken, especially regarding those with vision-threatening diseases requiring treatment.