Purpose: The aim of this study is to analyze and summarize the diverse ocular manifestations in probands with pathogenic or likely pathogenic (P/LP) variants in NF1 and NF2. Methods: Variants in NF1 and NF2 were selected from in-house exome sequencing and whole genome sequencing of individuals with different eye conditions. P/LP variants were assessed by multiple bioinformatic tools, Sanger sequencing confirmation, co-segregation analysis, and finally classified based on ACMG/AMP criteria. All the available clinical data were summarized and further analyzed. Results: A total of ten P/LP variants in NF1 and NF2 were identified in 11 unrelated cases with various eye conditions, including three NF2 variants in four cases and seven NF1 variants in seven cases. The four patients with NF2 variants had clinical presentations similar to familial exudative vitreoretinopathy (FEVR), and macular or retinal dystrophy at the initial visit. After the identification of NF2 variants, a follow-up examination on two of the four identified typical retinal changes of NF2, including epiretinal membrane (ERM) and retinal hamartoma. Interestingly, one case had complicated ocular phenotypes (ERM plus retinal hamartoma, retinoschisis, and congenital stationary night blindness) due to pathogenic variants in three genes (NF2, RS1, and NYX) as well as bilateral vestibular schwannomas, spinal ependymoma and multiple schwannomas associated with NF2 variants. Of the seven cases with NF1 variants, five with signs and symptoms mimicking strabismus, FEVR, retinitis pigmentosa, Coats disease, and morning glory syndrome, respectively, while the remaining two had typical optic nerve glioma with histopathological confirmation. Café-au-lait macules or freckling were not noticed by the patients or ophthalmologists, but such skin changes were actually present in four of the seven cases on follow-up examination, which could be easily neglected if neurofibromatosis is not realized on the initial visit. Conclusions: This study extends the spectrum of ocular phenotypes of NF. Variable ocular changes may present as the initial sign of neurofibromatosis. Awareness of such association, combined with visualization of skin, systemic MRI scan, and gene test, may be helpful in the diagnosis of such diseases and facilitate early identification of vital systemic complication.

Background: The usage of the light emitting diode (LED) has been increasingly applied in the illumination setting and electronic equipment. However, the effect of LED lights on the retina remains unclear. In this study, we observed and analyzed the impact of white LED lights at different intensities on the function and morphology of rat retinas.

Methods: Thirty-six Sprague-Dawley rats weighing 150–180 g were randomly divided into six groups (n=6 in each group) including a normal control (NC) group, 4 white LED groups at different light intensities (4,000, 6,000, 7,000, and 10,000 lux), and an ultraviolet B (UVB) lighting group (302 nm, 1,000 μw/cm²). After 24 hours of continuous illumination, full-field flash electroretinogram (FERG) and pathological examination were performed in each group.

Results: As revealed by FERG, the impairment of retinal function gradually worsened with the increase of LED light intensity. In contrast, the UVB group had the most severe retinal function impairment. Particularly, the functional damage of rod cells and inner nuclear layer cells was the main FERG finding in each group. In the NC group, the retina had typical morphologies featured by well-defined structures, clearly visible border between the inner and outer segments, and neatly arranged inner and outer nuclear layer cells. After 24 hours of illumination, the inner and outer parts of the retina in the 4,000 lux group were still neatly arranged, along with a clear border; however, the inner and outer nuclear layers were randomly arranged, and some irregular nuclei and cells were lost. The damage of the internal and external retinal segments and the internal and external nuclear layers became more evident in the 6,000 lux group, 7,000 lux group, and 10,000 lux group. The UVB group had a more obviously disordered arrangement of inner and outer nuclear layers and loss of cells.

Conclusions: Continuous exposure to white LED light can cause structural and functional damage to rat retinas, and such damage is related to the intensity of illumination. Therefore, the risk of retinal damage should be considered during LED illumination, and proper LED illumination intensity may help to maintain eye health.

Background: To investigate the effect of sirolimus (SRL) eye drops on acute alkali-burn-induced corneal neovascularization (CNV) and explore its possible mechanism.

Methods: A total of 57 male Sprague-Dawley rats weighing 160–180 g were randomly divided into four groups including a normal control group (NC group, n=12), an untreated alkali-burned model control group (MC group, n=15), a blank eye drop treatment group (BT group, n=15), and an SRL eye drop treatment group (ST group, n=15). Corneal inflammation and CNV were observed and scored under a slit-lamp microscope 3, 7, and 14 days after alkali exposure. Three rats were randomly sacrificed in each group before modeling and 3, 7, 14 days after modeling, and the corneas of right eyes were harvested for Western blotting to compare the expression levels of VEGFR2 and caspase-3.

Results: Corneal inflammation scoring showed that the corneal edema and conjunctival congestion were severe in the MC, BT, and ST groups 1 day after alkali exposure but were alleviated at day 3. The corneal transparency was significantly higher in the ST group than in the MC and BT groups at days 7 (F=9.77, P<0.05) and 14 (F=5.81, P<0.05). At day 1, the corneal limbal vascular network was markedly filled. SNV was obvious at days 3, 7, and 14. The new blood vessels were shorter and sparser in the ST group than in the MC and BT groups, and the CNV scores showed significant differences among these groups (day 3: F=8.60, P<0.05; day 7: F=11.40, P<0.05; and day 14: F=41.59, P<0.01). Western blotting showed that the expressions of VEGFR2 and caspase-3 were low before modeling and showed no significant difference among the different groups (F=0.52, P>0.05; F=0.98, P>0.05). The corneal expression of VEGFR2 became significantly higher in the MC and BT groups than in the ST group 3, 7, and 14 days after alkali exposure, and there were significant differences in relative gray-scale values among these groups (day 3: F=32.16, P<0.01; day 7: F=85.96, P<0.01; day 14: F=57.68, P<0.01). The increase in the corneal expression of caspase-3 was significantly larger in the ST group than in the MC and BT groups at days 3, 7, and 14, and there were significant differences in relative gray-scale values among groups (day 3: F=32.16, P<0.01; day 7: F=53.02, P<0.01; day 14: F=38.67, P<0.01).

Conclusions: SRL eye drops can alleviate acute alkali-burn-induced corneal inflammation and inhibit alkali-burn-induced CNV in rat models. It can reduce VEGFR2 expression and increase caspase-3 expression in the corneal tissue, which may contribute to the inhibition of alkali-burn-induced CNV.