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We report a case of methanol blindness. Ophthalmoscopic examination disclosed swelling in the disc margins extending along the adjacent retinal nerve fiber layer. Although this optic neuropathy is now rare, prompt diagnosis and proper treatment in the acute phase can dramatically improve the prognosis.

The manifestations of the ocular toxicity of systemic corticosteroids include posterior subcapsular cataracts and glaucoma. We describe 14 cases of serous detachment of the macula due to central serous chorioretinopathy in patients given long-term steroid therapy, which may be another potential ocular side effect of corticosteroid.The 14 (9 men and 5 women) patients were aged from 39 to 55 year old. Their systemic diseases were allergic thrombopenic purpura, optic neuritis, kidney or heart transplant, Churg and Strauss vasculitis, facial palsy, rheumatoid arthritis, systemic lupus and a kidney tumor. None of the patients had hypertension.Serous detachment occurred between 6 days and 10 years after the start of steroid treatment. The higher the doses, the earlier the onset of ocular disease. All patients were symptomatic, with rapid onset of blurred vision. Serous detachment was bilateral in two cases. The fluorescein angiographic finding was in most cases a single small focal hyperfluorescent leak from the retinal pigment epithelium which appeared early in the angiogram and increased in size and intensity. No diffuse degradation of the retinal pigment epithelium was seen on the fluorescein angiogram. Five patients underwent laser photocoagulation of the leaking area followed by resorption of subretinal fluid. In other patients, the symptoms disappeared as the doses of steroid were reduced.The pathogenesis of central serous chorioretinopathy remains unclear and is controversial. Corticosteroids are known to worsen the prognosis of idiopathic central serous chorioretinopathy, and serous detachment has been reported after renal transplantation. In most of these cases, chorioretinopathy was combined with diffuse leakage from the choriocapillaris. We discuss the relationship between steroid therapy and focal leakage as seen in idiopathic central serous chorioretinopathy. In conclusion, we describe 14 cases of central serous retinopathy whose clinical and fluorescein angiography were fairly typical, without obvious diffuse degradation of the retinal pigment epithelium. All these patients had been given long-term steroid therapy for various diseases.

Leber's hereditary optic neuropathy (LHON) is the most frequent mitochondrial disease and was the first to be genetically defined by a point mutation in mitochondrial DNA (mtDNA). A molecular diagnosis is achieved in up to 95% of cases, the vast majority of which are accounted for by 3 mutations within mitochondrial complex I subunit-encoding genes in the mtDNA (mtLHON). Here, we resolve the enigma of LHON in the absence of pathogenic mtDNA mutations. We describe biallelic mutations in a nuclear encoded gene, DNAJC30, in 33 unsolved patients from 29 families and establish an autosomal recessive mode of inheritance for LHON (arLHON), which to date has been a prime example of a maternally inherited disorder. Remarkably, all hallmarks of mtLHON were recapitulated, including incomplete penetrance, male predominance, and significant idebenone responsivity. Moreover, by tracking protein turnover in patient-derived cell lines and a DNAJC30-knockout cellular model, we measured reduced turnover of specific complex I N-module subunits and a resultant impairment of complex I function. These results demonstrate that DNAJC30 is a chaperone protein needed for the efficient exchange of complex I subunits exposed to reactive oxygen species and integral to a mitochondrial complex I repair mechanism, thereby providing the first example to our knowledge of a disease resulting from impaired exchange of assembled respiratory chain subunits.

Objective: This work aimed to compare the evolution of visual outcomes in Leber hereditary optic neuropathy (LHON) patients treated with intravitreal gene therapy to the spontaneous evolution in prior natural history (NH) studies.Design: A combined analysis of two phase three randomized, double-masked, sham-controlled studies (REVERSE and RESCUE) and their joint long-term extension trial (CLIN06) evaluated the efficacy of rAAV2/2-ND4 vs. 11 pooled NH studies used as an external control.Subjects: The LHON subjects carried the m.11778G>A ND4 mutation and were aged ≥15 years at onset of vision loss.Methods: A total of 76 subjects received a single intravitreal rAAV2/2-ND4 injection in one eye and sham injection in the fellow eye within 1 year after vision loss in REVERSE and RESCUE. Both eyes were considered as treated due to the rAAV2/2-ND4 treatment efficacy observed in the contralateral eyes. Best corrected visual acuity (BCVA) from REVERSE, RESCUE, and CLIN06 up to 4.3 years after vision loss was compared to the visual acuity of 208 NH subjects matched for age and ND4 genotype. The NH subjects were from a LHON registry (REALITY) and from 10 NH studies. A locally estimated scatterplot smoothing (LOESS), non-parametric, local regression model was used to modelize visual acuity curves over time, and linear mixed model was used for statistical inferences.Main Outcome Measures: The main outcome measure was evolution of visual acuity from 12 months after vision loss, when REVERSE and RESCUE patients had been treated with rAAV2/2-ND4.Results: The LOESS curves showed that the BCVA of the treated patients progressively improved from month 12 to 52 after vision loss. At month 48, there was a statistically and clinically relevant difference in visual acuity of −0.33 logarithm of the minimal angle of resolution (LogMAR) (16.5 ETDRS letters equivalent) in favor of treated eyes vs. NH eyes (p < 0.01). Most treated eyes (88.7%) were on-chart at month 48 as compared to 48.1% of the NH eyes (p < 0.01). The treatment effect at last observation remained statistically and clinically significant when adjusted for age and duration of follow-up (−0.32 LogMAR, p < 0.0001).Conclusions: The m.11778G>A LHON patients treated with rAAV2/2-ND4 exhibited an improvement of visual acuity over more than 4 years after vision loss to a degree not demonstrated in NH studies.Clinical Trial Registration: NCT02652767, NCT02652780, NCT03406104, and NCT03295071.

Objective To compare the diagnostic performance of an artificial intelligence deep learning system with that of expert neuro-ophthalmologists in classifying optic disc appearance. Methods The deep learning system was previously trained and validated on 14,341 ocular fundus photographs from 19 international centers. The performance of the system was evaluated on 800 new fundus photographs (400 normal optic discs, 201 papilledema [disc edema from elevated intracranial pressure], 199 other optic disc abnormalities) and compared with that of 2 expert neuro-ophthalmologists who independently reviewed the same randomly presented images without clinical information. Area under the receiver operating characteristic curve, accuracy, sensitivity, and specificity were calculated. Results The system correctly classified 678 of 800 (84.7%) photographs, compared with 675 of 800 (84.4%) for Expert 1 and 641 of 800 (80.1%) for Expert 2. The system yielded areas under the receiver operating characteristic curve of 0.97 (95% confidence interval [CI] = 0.96-0.98), 0.96 (95% CI = 0.94-0.97), and 0.89 (95% CI = 0.87-0.92) for the detection of normal discs, papilledema, and other disc abnormalities, respectively. The accuracy, sensitivity, and specificity of the system's classification of optic discs were similar to or better than the 2 experts. Intergrader agreement at the eye level was 0.71 (95% CI = 0.67-0.76) between Expert 1 and Expert 2, 0.72 (95% CI = 0.68-0.76) between the system and Expert 1, and 0.65 (95% CI = 0.61-0.70) between the system and Expert 2. Interpretation The performance of this deep learning system at classifying optic disc abnormalities was at least as good as 2 expert neuro-ophthalmologists. Future prospective studies are needed to validate this system as a diagnostic aid in relevant clinical settings. ANN NEUROL 2020;88:785-795.