Could internal limiting membrane peeling before Voretigen neparvovec-ryzl subretinal injection prevent focal chorioretinal atrophy?

Purpose: To report the effect of internal limiting membrane (ILM) peeling prior to Voretigen Neparvovec-ryzl (VN) subretinal injection on focal chorioretinal atrophy development in patients presenting with RPE65-mediated Leber congenital amaurosis (LCA). Design: Retrospective case series. Methods: Three patients who underwent bilateral subretinal VN injection for RPE65-mediated LCA were followed up for 18-24 months. ILM peeling was performed unilaterally in patients 1 and 2 and bilaterally in patient 3. Chorioretinal atrophy was identified on fundus biomicroscopy, non-mydriatic retinography and/or ultrawide field fundus imaging. Best corrected visual acuity (BCVA), spectral-domain optical coherence tomography (SD-OCT), visual fields, full-field stimulus threshold (FST) and visual functioning questionnaire score (NEI-VFQ-25) were reported. Outcome measures were changes in BCVA, visual fields, FST, NEI-VFQ-25, and chorioretinal atrophy location. Results: Chorioretinal atrophy at the injection site exclusively developed in eyes which did not undergo prior ILM peeling. In patient 3, bilateral pre-operative nummular chorioretinal alterations progressed toward epithelial atrophic patches in the mid and extreme retinal periphery 18 months after VN injection. BCVA and visual fields improved bilaterally. NEI_VFQ 25 remained stable in patient 1 and improved in patient 2 and 3. FST test improved bilaterally in patient 3. Conclusions: ILM peeling prior to VN injection seems to be a smoother and safer technique to administer VN treatment and may prevent secondary focal atrophy development at the injection site. However, another type of more extended chorioretinal atrophy might exist and could be related to LCA evolution or to incompletely understood adverse effect of VN product.

Retinal microvascular changes in unilateral functional amblyopia detected by oct-angiography and follow-up during treatment.

OBJECTIVE: To evaluate the macular microvascular changes using optical coherence tomographic angiography (OCT-A) in children with unilateral amblyopia and their reversibility during treatment. METHODS: Patients with unilateral strabismic or anisometropic amblyopia or residual amblyopia from early congenital cataract surgery, examined between October 2019 and March 2021, were included. Vessel density and perfusion density in the superficial capillary plexus and area, perimeter and circularity of the foveal avascular zone (FAZ) were analysed using OCT-A in amblyopic eyes, contralateral eyes and control group healthy eyes. Correlation analyses between the microvascular parameters and the visual acuity were performed. In a pilot study on a few patients from the amblyopic cohort, longitudinal follow-up during treatment was also performed. RESULTS: A total of 128 eyes of 64 patients were included: 32 amblyopic eyes compared with 32 contralateral eyes and 64 control eyes. Vessel density and perfusion density in the superficial capillary plexus were significantly lower in amblyopic eyes compared to control eyes in 6 × 6 mm (p < 0.02) and 3 × 3 mm (p < 0.01) scans. Correlation analyses showed a linear decrease in vessel density and perfusion density with decreasing visual acuity. The microvascular changes observed were reversible with the occlusion treatment of amblyopia (p < 0.001). CONCLUSIONS: The study found a decrease in vessel density and perfusion density in the macula of children with unilateral functional amblyopia. These microvascular changes were correlated with visual acuity and appeared to be reversible with treatment of amblyopia. On the whole, OCT-A appears to be a relevant complementary examination when it comes to diagnosing and monitoring functional amblyopia.

LONG-TERM MICROVASCULAR REMODELING AND CYSTIC CHANGES AFTER RETINAL DETACHMENT TREATED WITH SILICON OIL TAMPONADE.

PURPOSE: To determine the long-term microvascular alterations associated with macular cystic changes after retinal detachment surgery with silicone oil tamponade. METHODS: The results of two optical coherence tomography angiographies performed at 11 months and 38 months after silicone removal were retrospectively analyzed for 30 eyes. The data were compared between both measurements and between eyes with macular cysts (MC+) and without macular cysts (MC-). Two patterns of cysts were identified and compared: cysts exclusively involving the inner nuclear layer (INLc) and cysts present in all retinal layers. RESULTS: At both end points, 20 eyes (67%) presented with macular cysts, 12 of them (40%) had INLc. At the first end point, vascular density of superficial capillary plexus was higher and superficial foveal avascular zone was smaller in MC+ eyes than in MC- eyes (P = 0.04 and P = 0.017, respectively). At the second end point, vascular density of superficial capillary plexus significantly decreased in MC+ eyes as compared with the first end point (P < 0.001) and superficial foveal avascular zone enlarged (P < 0.001). Macular central thickness decreased between follow-ups only in eyes with INLc (P < 0.01). The final best-corrected visual acuity was better in eyes with INLc than in eyes with cysts present in all retinal layers (P < 0.01). There was no difference between the final best-corrected visual acuity in eyes with INLc and MC- eyes. CONCLUSION: Macular cysts are a common finding long after silicon removal. Vascular remodeling seems characterized by an initial increase of the vascular density of superficial capillary plexus in eyes with cysts, which is followed by its progressive decrease. The INLc is the most common pattern of cysts. They are associated with a progressive decrease of the central macular thickness without visual impairment.

State of the Art in Robot-Assisted Eye Surgery.

Despite the advantages that robot-assisted surgery can offer to patient care, its use in ophthalmic surgery has not yet progressed to the extent seen in other fields. As such, its use remains limited to research environments, both basic and clinical. The technical specifications for such ophthalmic surgical robots are highly challenging, but rapid progress has been made in recent years, and recent developments in this field ensure that the use of this technology in operating theatres will soon be a real possibility. Fully automated ocular microsurgery, carried out by a robot under the supervision of a surgeon, is likely to become our new reality. This review discusses the use of robot-assisted ophthalmic surgery, the recent progress in the field, and the necessary future developments which must occur before its use in operating theatres becomes routine.

Intravenous high-dose methotrexate based systemic therapy in the treatment of isolated primary vitreoretinal lymphoma: An LOC network study.

The treatment of primary vitreoretinal lymphoma (PVRL) remains controversial regarding the use of local, systemic, or combined treatments. The aim of this study was to analyze the efficacy and toxicity of intravenous high-dose methotrexate (IV HD-MTX) based systemic therapy in a uniformly treated population of PVRL patients. From a nationwide French database, we retrospectively selected 59 patients (median age: 70 years, median Karnofsky Performance Status: 90%) with isolated PVRL at diagnosis who received first-line treatment with HD-MTX between 2011 and 2018. 8/59 patients also received a local treatment. No deaths or premature discontinuations of MTX due to toxicity were reported. A complete response was obtained in 40/57 patients after chemotherapy. Before treatment, IL-10 was elevated in the aqueous humor (AH) or in the vitreous in 89% of patients. After treatment, AH IL-10 was undetectable in 87% of patients with a CR/uCR/PR and detectable in 92% of patients with PD/SD. After a median follow-up of 61 months, 42/59 (71%) patients had relapsed, including 29 isolated ocular relapses as the first relapse and a total of 22 brain relapses. The median overall survival, progression-free survival, ocular-free survival and brain-free survival were 75, 18, 29 and 73 months, respectively. IV HD-MTX based systemic therapy as a first-line treatment for isolated PVRL is feasible, with acceptable toxicity, even in an elderly population. This strategy seems efficient to prevent brain relapse with prolonged overall survival. However, the ocular relapse rate remains high. New approaches are needed to improve local control of this disease, and ocular assessment could be completed by monitoring AH IL-10.

Severe South American ocular toxoplasmosis is associated with decreased Ifn-γ/Il-17a and increased Il-6/Il-13 intraocular levels.

In a cross sectional study, 19 French and 23 Colombian cases of confirmed active ocular toxoplasmosis (OT) were evaluated. The objective was to compare clinical, parasitological and immunological responses and relate them to the infecting strains. A complete ocular examination was performed in each patient. The infecting strain was characterized by genotyping when intraocular Toxoplasma DNA was detectable, as well as by peptide-specific serotyping for each patient. To characterize the immune response, we assessed Toxoplasma protein recognition patterns by intraocular antibodies and the intraocular profile of cytokines, chemokines and growth factors. Significant differences were found for size of active lesions, unilateral macular involvement, unilateral visual impairment, vitreous inflammation, synechiae, and vasculitis, with higher values observed throughout for Colombian patients. Multilocus PCR-DNA sequence genotyping was only successful in three Colombian patients revealing one type I and two atypical strains. The Colombian OT patients possessed heterogeneous atypical serotypes whereas the French were uniformly reactive to type II strain peptides. The protein patterns recognized by intraocular antibodies and the cytokine patterns were strikingly different between the two populations. Intraocular IFN-γ and IL-17 expression was lower, while higher levels of IL-13 and IL-6 were detected in aqueous humor of Colombian patients. Our results are consistent with the hypothesis that South American strains may cause more severe OT due to an inhibition of the protective effect of IFN-γ.

Retreatment by series of three intravitreal injections of ranibizumab in neovascular age-related macular degeneration: long-term outcomes.

BACKGROUND: The purpose of this study was to analyze the results of a retreatment regimen using a series of three monthly intravitreal ranibizumab injections (IVR), instead of one injection, and to determine if this treatment scheme can safely reduce the number of injections and the number of visits compared to the widely used PrONTO study retreatment protocol. METHODS: >Sixty-six eyes of 60 patients with exudative age-related macular degeneration (AMD) were included. The mean follow-up period was 27 months (range, 11-48 months). The mean age of the patients was 79 years (range, 65-93 years). All patients received three initial IVRs, and were retreated with a new series of three monthly IVRs when needed. The retreatment criteria were: visual loss of ≥5 ETDRS letters and/or signs of retinal exudation on OCT, new macular hemorrhage, expansion of new vessels. Follow-up visits were conducted 1 month after the last IVR of each series, and renewed on a monthly basis when no retreatment was required. Each visit included a comprehensive ophthalmological examination with BCVA measurement and OCT examination. RESULTS: Mean VA did not improve during follow-up (53.18 letters at the initial visit versus 54.18 at the last visit, p > 0.05). However, VA stabilized or improved in 66.6 % of the eyes. A gain of ≥15 letters was observed in 28.8 % of eyes. On average, over 2 years, the number of IVRs was five per year, and the number of follow-up visits was four per year. CONCLUSION: Even if no gain in VA is observed after 2 years, this treatment regimen reduces the number of IVRs and control visits. The proportion of patients with a VA gain of three lines or more was smaller than the one reported in the original PrONTO study, but higher than the rates reported in other studies implementing the PrONTO recommendations in everyday practice. The benefit of the three IVR retreatment scheme should be prospectively studied and compared to the PRN regimen.

Central nervous system abnormalities in patients with PMP22 gene mutations: a prospective study.

BACKGROUND: Mutations of the peripheral myelin protein-22 (PMP22) gene are the most common cause of inherited disease of the peripheral nervous system (PNS), with its deletion resulting in hereditary neuropathy with liability to pressure palsies (HNPP), and its duplication inducing Charcot-Marie-Tooth 1A (CMT1A) disease. Although mainly expressed in the PNS, PMP22 mRNA and protein are also present in the central nervous system (CNS). OBJECTIVE: To investigate whether patients with PMP22 mutations present with CNS abnormalities. METHODS: Fifteen patients with HNPP and 15 patients with CMT1A disease were prospectively included and their brain MRI and neuropsychological assessment were compared with those of healthy subjects. We evaluated, in particular, the volumes of grey and white matter (GM and WM) and looked for metabolic changes using spectroscopy, and abnormal architecture using fractional anisotropy (FA) measurement. A post mortem examination of the CNS of a patient with PMP22 gene duplication was also performed. RESULTS: We found a decrease in the volume of WM in 70% of patients, a reduced creatine level in WM in 28% and a cognitive impairment in 70%. FA was significantly altered in several areas of WM, including the columns of the fornix. The results for WM volume, creatine level in WM and cognitive testing showed that 47% of patients (patients with HNPP and those with CMT1A) presented with at least two abnormal results. Pathological examination of the brain of a patient with PMP22 gene duplication showed diffuse hypomyelination sparing the U fibres. CONCLUSIONS: This study demonstrates that altered PMP22 gene expression induces significant CNS alterations in patients with HNPP and CMT1A, including cerebral WM abnormalities and cognitive impairment.

Lyme optic neuritis.

Lyme optic neuritis (ON) is a rare disease and only a few cases have been reported. We describe two cases of isolated Lyme ON, one with recurrence 9 months after the appearance of initial symptoms. Diagnosis criteria for multiple sclerosis and neuromyelitis optica were not met. The etiological diagnosis was based on European case definition criteria for neuroborreliosis. Both patients had positive serum and cerebrospinal fluid serology, a positive intrathecal anti-Borrelia antibody index, and a good outcome on ceftriaxone. Specific diagnosis of Lyme ON is important since improvement of visual acuity is possible with specific antibiotherapy, even after many months.

[Ocular side effects of steroids and other immunosuppressive agents]. / Complications ophtalmologiques des immunosuppresseurs et des corticoïdes.

The increasing use of immunosuppressive (IS) drugs in transplants or in systemic diseases, implies a long period of treatment and to be aware of possible side effects. These drugs can be used alone or in combination with steroids. This review deals with the issue of ocular side effects of the most used IS drugs, including steroids. Data were collected from Medline using Pubmed software. We first describe specific complication of each drug and then conclude on major common toxicity represented by opportunistic infections and induced cancers.

Optical coherence tomography in neuromyelitis optica.

BACKGROUND: Neuromyelitis optica (NMO) is an inflammatory disease with combined features of optic neuritis and myelitis. This pathologic entity may induce severe disability, including visual loss and paraplegia. Other than clinical follow-up, there is no marker for severity of the disease. OBJECTIVES: To evaluate the use of optical coherence tomography (OCT) in NMO and to determine whether this new technique could be a good marker of axonal loss in NMO. DESIGN: Cross-sectional study. PARTICIPANTS: Thirty-five patients with NMO or at a high risk for NMO (having optic neuritis or myelitis and who are positive for NMO antibody) were prospectively studied. Fifteen healthy individuals served as control subjects. MAIN OUTCOME MEASURE: All patients underwent a complete ophthalmologic evaluation, including OCT, funduscopy, and visual field, visual acuity, and visual evoked potential testing. Expanded Disability Status Scale scores were assessed but without the visual data. Correlations between the visual test results and demographic or clinical characteristics were evaluated. RESULTS: Optical coherence tomography and visual field data were available for only 32 patients because 3 patients were blind. The mean retinal nerve fiber layer thickness was significantly reduced in patients with NMO compared with controls (P < .001). We found good correlation between the OCT results and visual field testing. We also found weak correlation between OCT results and both visual acuity and visual evoked potential latencies. We did not find any correlation between OCT results and age, sex, or disease duration. In contrast, retinal nerve fiber layer thickness was closely correlated with the Expanded Disability Status Scale score (P < .001). CONCLUSIONS: Optical coherence tomography results are significantly altered in patients with NMO. Optical coherence tomography is easy to perform, and the results are well correlated with visual acuity and visual field findings. It could be considered a marker of axonal loss because we found good correlation between OCT and the Expanded Disability Status Scale score. These preliminary results will need to be confirmed in a longitudinal prospective study.

Coronal alignment of the lower limb.

BACKGROUND: The coronal alignment of the lower limb is important for knee reconstruction procedures. However, normal alignment is hard to define because of its wide variation among normal individuals. Our hypothesis was that the variation in the normal anatomy as assessed by radiography is greater than commonly accepted. METHODS: We performed anteroposterior long-leg radiographs on 100 Caucasian patients without any known knee abnormality, to determinate the femorotibial angle, coronal orientation of the distal femoral condyles, and coronal orientation of the proximal tibial condyles. All measurements were performed by the same experienced knee surgeon. RESULT: The mean values observed were close to the values commonly described in the Caucasian population. However, only 15-20% of the cases met the mean values of Moreland et al. (1987) for the individual items, and only 2 cases had the exact normal values. There was a wide variation for all angles measured, with a standard deviation higher than the mean value. INTERPRETATION: The variation in the lower limb axes is wider than commonly believed. There is a need for individual knee reconstruction which takes the specific knee axes of the patient to be operated into account.