The formation of metabolite fibrillar assemblies represents a paradigm shift in the study of human metabolic disorders. Yet, direct clinical relevance has been attributed only to metabolite crystals. A notable example for metabolite crystallization is calcium oxalate crystals observed in various diseases, including primary hyperoxaluria. We unexpectedly observed retinal damage among young hyperoxaluria patients in the absence of crystals. Exploring the possible formation of alternative supramolecular organizations and their biological role, here we show that oxalate can form ordered fibrils with no associated calcium. These fibrils inflict intense retinal cytotoxicity in cultured cells. A rat model injected with oxalate fibrils recaptures patterns of retinal dysfunction observed in patients. Antibodies purified from hyperoxaluria patient sera recognize oxalate fibrils regardless of the presence of calcium. These findings highlight a new molecular basis for oxalate-associated disease, and to our knowledge provide the first direct clinical indication for the pathogenic role of metabolite fibrillar assemblies.

Amyloid-β (Aβ), reported as a significant constituent of drusen, was implicated in the pathophysiology of age-related macular degeneration (AMD), yet the identity of the major pathogenic Aβ species in the retina has remained hitherto unclear. Here, we examined the in-vivo retinal impact of distinct supramolecular assemblies of Aβ. Fibrillar (Aβ40, Aβ42) and oligomeric (Aβ42) preparations showed clear biophysical hallmarks of amyloid assemblies. Measures of retinal structure and function were studied longitudinally following intravitreal administration of the various Aβ assemblies in rats. Electroretinography (ERG) delineated differential retinal neurotoxicity of Aβ species. Oligomeric Aβ42 inflicted the major toxic effect, exerting diminished ERG responses through 30 days post injection. A lesser degree of retinal dysfunction was noted following treatment with fibrillar Aβ42, whereas no retinal compromise was recorded in response to Aβ40 fibrils. The toxic effect of Aβ42 architectures was further reflected by retinal glial response. Fluorescence labelling of Aβ42 species was used to detect their accumulation into the retinal tissue. These results provide conceptual evidence of the differential toxicity of particular Aβ species in-vivo, and promote the mechanistic understanding of their retinal pathogenicity. Stratifying the impact of pathological Aβ aggregation in the retina may merit further investigation to decipher the pathophysiological relevance of processes of molecular self-assembly in retinal disorders.

Purpose To characterize quantitative differences among ophthalmologic emergency room (OER) encounters at Rambam Health Care Campus during a 6-week complete lockdown at the peak of the first COVID-19 wave as compared to a corresponding uneventful period a year earlier. Methods A retrospective chart analysis of all OER encounters during the lockdown and non-lockdown period was conducted. Patients were stratified into primary ophthalmological conditions (OER visits) and cases in which ophthalmologic consultations were requested by a non-ophthalmologist (OER consultations). The following parameters were compared: total number of cases, age, gender, chief complaint/diagnosis categorized into major entities, and discharge vs. hospitalization. For continuous variables a t-test was used and for categorical variables a chi-squared or Fisher’s exact test was used. A 2-sided p value <0.05 was considered statistically significant. Results The total number of patients in the lockdown and non-lockdown groups was 486 and 992, respectively, showing a 51% decrease in visits during lockdown. In the non-lockdown and lockdown groups 56% and 61% of patients were male (p = 0.07), with an average age of 42 (range 0–97, SD 23) and 43 (range 0–90, SD 22) years, respectively (p = 0.44). No statistically significant proportional increase was found for any diagnostic category between the OER visits (p = 0.07) and OER consultation groups (p = 0.77). Nevertheless, analysis revealed a non-significant increase in the proportion of eye trauma from 14.8% to 21.2%, and reduction in eyelid conditions from 10.7% to 5.8%. The total number of OER visits demanding urgent intervention on admission was 43 (non-lockdown) and 24 (lockdown), while hospitalization ratio (hospitalizations/visits) was 8.8% and 10.6%, respectively (p = 0.44). Conclusions During the COVID-19 lockdown the guideline for patients in Israel was to avoid unnecessary hospital visits. Since patients tended to avoid the OER rather uniformly regardless of their specific eye condition, determining the risk-benefit of such recommendations and identifying high-risk sub-populations are critical public health issues.

Purpose Schistosomiasis, one of the most important parasitic diseases in humans, is caused by the trematode parasites. Common manifestations include gastrointestinal and genitourinary symptoms while ophthalmologic involvement is rare. Here we report a case of retinal vein occlusion and neuroretinitis secondary to a schistosomiasisis infection. Observations A healthy 23-year-old man presented with headache and decreased vision in his right eye. Ophthalmic examination revealed a swollen disc, engorged retinal veins with retinal hemorrhages in all quadrants and macular edema with hard exudates (‘macular star’). Fluorescein Angiography demonstrated a hot disk and an irregular pattern of filling defects along a major retinal vein. Further questioning revealed that a few months earlier, the patient had returned from an endemic area and was found seropositive for schistosomiasis. Conclusion In this case of neuroretinitis and secondary retinal venous stasis, the presumed underlying mechanism is associated with embolization of Schistosoma eggs or deposition of immune complexes. Although ophthalmic manifestations of schistosomiasis are rare, awareness should be maintained especially among world-travelers with unusual ocular findings.

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