Improved Rod Sensitivity as Assessed by Two-Color Dark-Adapted Perimetry in Patients With RPE65-Related Retinopathy Treated With Voretigene Neparvovec-rzyl.

Purpose: The purpose of this study was to evaluate rod-mediated function with two-color dark-adapted perimetry (2cDAP) in patients with RPE65-related retinopathy treated with voretigene neparvovec-rzyl. Methods: Following dilation and dark adaptation, 2cDAP and FST were performed. The 2cDAP was measured on an Octopus 900 perimeter (Haag-Streit) with cyan (500 nm wavelength) and red (650 nm wavelength) stimuli. Hill of vision (HOV) analysis was performed on 2cDAP perimetry with Visual Field Modeling and Analysis (VFMA). Full field threshold stimulus testing (FST) was also measured as a secondary measure of rod-mediated function, and assessed on a Diagnosys Espion with the ColorDome stimulator (Diagnosys LLC). Results: Eight eyes from 4 patients who were treated with voretigene bilaterally had rod function assessed by 2cDAP testing at least 1 year after treatment. There was statistically significant improvement in 2cDAP following gene augmentation therapy. HOV VFMA analysis showed widespread improvements that extended beyond the treatment bleb and statistically significant improvement in HOV analysis volumetric measurements post-treatment to cyan and red stimuli. FST testing performed in six eyes from three patients demonstrated statistically significant improvement to all chromatic stimuli following treatment. Conclusions: These findings demonstrated statistically significant improvement in 2cDAP and FST following treatment with voretigene. Translational Relevance: These findings provide a sensitive method of assessing rod-mediated function in a topographic manner that may be useful in future clinical trials for inherited retinal dystrophies.

Advances in Vitreoretinal Surgery.

Advances in vitreoretinal surgery provide greater safety, efficacy, and reliability in the management of the several vitreoretinal diseases that benefit from surgical treatment. The advances are divided into the following topics: scleral buckling using chandelier illumination guided by non-contact visualization systems; sclerotomy/valved trocar diameters; posterior vitrectomy systems and ergonomic vitrectomy probes; chromovitrectomy; vitreous substitutes; intraoperative visualization systems including three-dimensional technology, systems for intraoperative optical coherence tomography, new instrumentation in vitreoretinal surgery, anti-VEGF injection before vitrectomy and in eyes with proliferative diabetic retinopathy, and new surgical techniques; endoscopic surgery; the management of subretinal hemorrhages; gene therapy; alternative techniques for refractory macular hole; perspectives for stem cell therapy and the prevention of proliferative vitreoretinopathy; and, finally, the Port Delivery System. The main objective of this review is to update the reader on the latest changes in vitreoretinal surgery and to provide an understanding of how each has impacted the improvement of surgical outcomes.

The first gene therapy for RPE65 biallelic dystrophy with voretigene neparvovec-rzyl in Brazil.

PURPOSE: To report the first Brazilian patient with RPE65 deficiency-inherited retinal dystrophy (RPE65-IRD) treated with voretigene neparvovec-rzyl (VN). METHODS: An adult patient with Leber congenital amaurosis-2 with a homozygous mutation in the RPE65 gene (p.Phe83Leu) was treated bilaterally with VN. The clinical and surgical aspects are described. The baseline and 4-month postoperative ophthalmologic examinations included measurement of the best-corrected visual acuity (BCVA), full-field stimulus threshold (FST) test, Octopus 900 semiautomated kinetic visual fields (VFs), and microperimetry. RESULTS: No complications developed in this patient. The BCVA remained stable. The full-field stimulus threshold test (FST) and VFs showed clinically significant improvements bilaterally. The patient reported significant improvements in the ability to perform daily activities, mainly for those requiring the VFs and vision in a low-luminescence environment. CONCLUSIONS: The treatments were beneficial for this patient who was homozygous for RPE65 p.Phe83Leu. The first VN treatments in an adult Brazilian patient in clinical practice showed measurable improvements in visual outcomes that were meaningful for the patient's daily activities. TRANSLATIONAL RELEVANCE: This case reinforces the clinical trial results and proves that the procedure is feasible in countries such as Brazil.

Injection pressure levels for creating blebs during subretinal gene therapy.

Retinal damage has been associated with increased injection pressure during subretinal gene therapy delivery in various animal models, yet there are no human clinical data regarding the pressures required to initiate and propagate subretinal blebs. This study characterized the intraoperative pressure levels for subretinal gene therapy delivery across eight retinal conditions. A total of 116 patients with retinal degenerative diseases have been treated with subretinal gene therapy at OHSU-Casey Eye Institute as of June 2020; seventy patients (60.3%) were treated using a pneumatic-assisted subretinal delivery system. All retinal blebs were performed using a 41-gauge injection cannula, and use of a balanced salt solution (BSS) "pre-bleb" prior to gene therapy delivery was performed at the discretion of the surgeon. Patient age and intraoperative data for BSS and vector injections were analyzed in a masked fashion for all patients who received pneumatic-assisted subretinal gene therapy. The median age of the patients was 35 years (range 4-70). No significant differences in injection pressures were found across the eight retinal conditions. In this study, patient age was shown to affect maximum injection pressures required for bleb propagation, and the relationship between age and pressure varied based on retinal condition. These data have important implications in optimizing surgical protocols for subretinal injections.

Adaptive optics ophthalmoscopy, multifocal ERG and OCTA in unique case of suspected torpedo maculopathy presenting with vitelliform lesion.

PURPOSE: To report the case of a ten-year old girl with torpedo maculopathy with a complete vitelliform lesion and describe associated optical coherence tomography (OCT), OCT angiography (OCTA), multifocal electroretinogram (ERG) and adaptive optics ophthalmoscopy (AOO) imaging of the lesion. OBSERVATIONS: An asymptomatic ten-year old girl with visual acuity of 20/15 OU was referred for evaluation of possible Best's disease of her left eye. The unilaterality, location, and shape of the lesion was consistent with torpedo maculopathy. OCT and autofluorescence (AF) revealed that the entire lesion was composed of subretinal hyperreflective material that was hyperautofluorescent, consistent with vitelliform material. Within the boundary of the lesion, OCTA showed reduced choriocapillaris density while adjacent to the lesion, the choriocapillaris density was slightly increased. Microperimetry demonstrated normal sensitivity in both eyes, electrooculograms (EOG) were normal and multifocal ERG showed symmetrical mildly supernormal amplitudes. Additionally, AOO demonstrated that nasal to the lesion there were clusters of hyper-reflective areas, and immediately adjacent to the lesion cones were poorly resolved. However, there was a return to more normal photoreceptor architecture outside of the lesion. CONCLUSIONS AND IMPORTANCE: Torpedo maculopathy lesions typically present with outer retinal attenuation and retinal pigmented epithelium (RPE) atrophy. Vitelliform material was recently observed for the first time in association with Torpedo maculopathy in a case report that described small vitelliform material at the periphery of the lesion. We report the second case of torpedo maculopathy associated with a vitelliform lesion and the first description of a torpedo lesion composed fully of presumed vitelliform material. We also describe findings of OCTA, multifocal ERG and AOO imaging in torpedo maculopathy with vitelliform lesion.

Intraoperative optical coherence tomographic findings in patients undergoing subretinal gene therapy surgery.

BACKGROUND: To analyze intraoperative OCT (iOCT) findings during subretinal gene therapy. METHODS: A single-center, retrospective, observational, case series study of twenty one eyes submitted to subretinal gene therapy. Intrasurgical high definition videos were included for analyzes. Cases with absence of iOCT video or unsuccessful bleb creation were excluded. Sharp needle tip (SNT) or blunted needle tip (BNT) and their interaction with neurosensory retina were evaluated. Presence of subretinal air bubbles, visible opened retinotomy, and medication reflux were also correlated and analyzed. RESULTS: Nineteen of twenty-one eyes were included. Of the two excluded eyes, subretinal bleb creation was unsuccessful in one and technical issues prevented OCT image acquisition in the other. Immediately before subretinal injection, needle indention/penetration of the neurosensory retina with temporary indentation of the RPE/choroid was evident in 16 (84%) of the 19 eyes. Complete RPE/choroid indentation was needed with BNT use compared to SNT (p = 0.0114). An open retinotomy was identified in 14 (74%) of 19 eyes at the conclusion of bleb injection and was more commonly associated with SNT (p = 0.0108). CONCLUSIONS: iOCT provides valuable real-time feedback of cross-sectional retinal anatomy during subretinal gene therapy surgeries. The type of needle tip and its use during the gene therapy procedure seems to influence in the bleb creation and presence of visible open retinotomy. Further studies of iOCT findings during gene therapy delivery procedures are likely to help refine the surgical technique.

Multimodal imaging of ring 14 syndrome associated maculopathy.

Background: Ring 14 syndrome is a rare chromosomal disorder characterized by a ring-shaped appearance of chromosome 14. Classically findings include distinct facial characteristics, refractory epilepsy, global development delay, muscular hypotonia and ocular abnormalities. Here we report a retinal multimodal imaging analyses of a ring chromosome 14 syndrome patient with associated macular pigmentary changes.Materials and Methods: Case report of an 11-year-old female with a history of refractory epilepsy since 3 months of age was diagnosed with ring 14 syndrome after karyotype at 8 months old. She presented with muscle weakness, mild intellectual delay, associated hyperopia and punctiform yellowish lesions. Multimodal imaging including fundus photography, red-free fundus photography, fundus auto-fluorescence and spectral-domain optical coherence tomography were used to assess this patient.Results: An 11-year-old female with ring 14 syndrome caused by the fusion of terminal breakpoints in both the short arm and long arm of chromosome 14 at p11.1 and q32.3, respectively. At eye exam, the best corrected visual acuity was 20/20 at both eyes with associated hyperopia. Macula showing scattered punctiform yellowish lesions, bright on red-free fundus photography and hyperautofluorescence dots in the same area. The SD-OCT showed normal characteristics at both eyes with the exception of localized irregularity of the RPE in an area associated with a macular yellow dots.Conclusions: Ring 14 syndrome can cause hyperopia and associated macular yellow dots visible at multimodal imaging analyses. Our data support regular eye examination for all patients with ring chromosome 14 syndrome.

Manifestation of a solitary retinal astrocytic hamartoma in a patient with Best macular dystrophy.

PURPOSE: To report the case of an adolescent male with a history of Best macular dystrophy and retinal astrocytic hamartoma. OBSERVATIONS: A 15 year old male with a history of Best macular dystrophy who had been followed by ophthalmology for 9 years was noted to have progressive enlargement of a superonasal peripapillary retinal lesion. Imaging and exam are consistent with a diagnosis of retinal astrocytic hamartoma. There were no extraocular signs or symptoms that were diagnostic of a phakamatosis. Genetic testing was positive for a mutation in BEST1, but not TSC1 or TSC2. CONCLUSIONS AND IMPORTANCE: Retinal astrocytic hamartoma is an unusual association with Best macular dystrophy, and this case highlights the balanced approach needed to navigate a potentially complex work-up.

[An advanced case of basosquamous carcinoma of the orbit: case report]. / Carcinoma basoescamoso avançado de órbita: relato de caso.

Basosquamous carcinoma is a rare tumor with features of both basal cell and squamous cell carcinoma, linked by a transition area. It is a rare epithelial neoplasm with a tendency for local recurrence. It also has a high incidence of distant metastasis, a condition that differentiates it from the basal cell carcinoma. In this case, the slow course of the infiltrative lesion associated to patient non-compliance to treatment led to a poor prognosis.