Clinical features of patients with mutations in genes for nanophthalmos.

BACKGROUND/AIMS: To distinguish the clinical feature of nanophthalmos (NNO) caused by mutations in protease serine 56 (PRSS56), membrane-type frizzled-related protein (MFRP), myelin regulatory factor (MYRF) and transmembrane protein 98 (TMEM98) and to evaluate the association between angle-closure glaucoma (ACG) and NNO. METHODS: Variants in those four genes were identified through exome sequencing/whole genome sequencing data, and bioinformatic analysis was conducted to identify pathogenic/likely pathogenic (P/LP) variants. This observational study comprehensively summarised ophthalmological data of 67 patients with NNO from 63 families. Ocular parameters from 68 eyes without surgical treatment were subjected to further analysis. RESULTS: Totally, 67 patients from 63 families harboured 57 P/LP variants in the four genes, including 30 in PRSS56 (47.6%), 23 in MFRP (36.5%), 5 in TMEM98 (7.9%) and 5 in MYRF (7.9%). ACG was present in 79.1% of patients. An analysis of ocular parameters from 68 eyes revealed that shorter axial length (AL), lower vitreous-to-AL ratios and severe foveal hypoplasia were associated with variants in PRSS56 and MFRP. Uveal effusion was more common in patients with PRSS56 variants, while retinitis pigmentosa was frequently observed in patients with MFRP variants. Patients with MYRF variants exhibited the thinnest retinal nerve fibre layer thickness. Patients with TMEM98 variants had an earlier average onset age of glaucoma. CONCLUSION: Variants in PRSS56 and MFRP are the most common genetic cause of NNO. ACG is a severe complication frequently observed in these patients. Earlier onset of ACG is observed in patients with dominant NNO, while foveal hypoplasia is more common in patients with recessive disease. Recognising these features is helpful in clinical care and genetic counselling.

Iris neovascularization and neurotrophic keratopathy following ultrasound cycloplasty in refractory glaucoma: case series.

BACKGROUND: Ultrasound cycloplasty is a noninvasive surgery used to reduce intraocular pressure in patients with glaucoma, with fewer severe complications. This report presents several cases of iris neovascularization and neurotrophic keratopathy following ultrasound cycloplasty. CASE PRESENTATION: Six patients diagnosed with refractory glaucoma underwent ultrasound cycloplasty at our clinic. Three cases developed iris neovascularization at postoperative day 3, week 2 and week 4 respectively, with intraocular pressure ranging from 12 to 24 mmHg. The other three cases developed neurotrophic keratopathy at postoperative week 3, week 6 and week 8 which completely healed within 60 days. CONCLUSIONS: Iris neovascularization and neurotrophic keratopathy can be triggered after ultrasound cycloplasty, which are uncommon and self-limited but potentially vision-threatening. Preoperative risk assessment and regular postoperative follow-up are recommended to manage complications effectively.

Development and Validation of an Internet-Based Remote Perimeter (Perimouse).

Purpose: We sought to validate the feasibility of Perimouse, an internet-based remote perimeter that allows for natural fixation and can be performed on most computers via a web page. Methods: In this cross-sectional study, Perimouse evaluated the visual field of 45 healthy people and 27 patients with primary open-angle glaucoma on a laptop. Participants used a mouse cursor to locate new dots on the screen that were determined by preset saccade vectors. A "click and confirm" strategy was used to eliminate the unwanted visual search. Dot brightness was either fixed at 12 dB in the suprathreshold program (screening program) or variable in the threshold program. We compared Perimouse outcomes with the Humphrey Field Analyzer (HFA) 24-2 Swedish Interactive Testing Algorithm standard program. Results: In the screening program, Perimouse showed moderate to high concordance with HFA. The intraclass coefficient ranged from 0.58 to 0.86 in different areas of Garway-Heath mapping. In the threshold program, normal subjects had threshold ranging from 19 to 16 dB, presenting sensitivity changes according to the "hill of vision". The test-retest difference was 0.09 dB. Habitual spectacle correction and environmental luminance (2-337 lux) had little impact on the central or peripheral threshold (P > 0.05). The correlation between Perimouse and HFA threshold sensitivity was strong (R = 0.950), although Perimouse mean defect was 4.40 dB higher than the HFA mean defect. Conclusions: Perimouse is a reliable visual field test that correlates strongly with HFA. It shows potential for population screening and monitoring visual field defects. Translational Relevance: Perimouse assesses the visual field using saccade vectors without eye trackers, enhancing its accessibility via a web page.

Continuous 24-hour intraocular pressure monitoring in normal Chinese adults using a novel contact lens sensor system.

AIMS: To investigate the physiological nyctohemeral intraocular pressure (IOP) rhythms of normal Chinese adults using a novel contact lens sensor system (CLS) that can output IOP in millimetres of mercury (mm Hg) continuously. METHODS: Fifty-nine eyes of 59 normal Chinese adults completed 24-hour IOP monitoring using the novel CLS. A descriptive analysis was conducted on the 24-hour IOP mean, peak and acrophase, trough and bathyphase, fluctuation, and mean amplitude of intraocular pressure excursion (MAPE). The continuous data were analysed at several periods (diurnal period, 08:00-20:00 hours; nocturnal period, 22:00-06:00 hours; sleep time, 0:00-06:00 hours), and compared between right and left eyes, males and females, and different age ranges (<30, and ≥30), respectively. RESULTS: Normal adults had a lower peak, higher trough, smaller fluctuation and smaller MAPE (p<0.05 for all comparisons) but non-significantly different mean (p=0.695) in the nocturnal period or sleep time compared with the diurnal period. The 24-hour IOP peak and trough showed the frequency of occurrence ranging from 1.69% to 15.25% at an interval of 2 hours. No IOP parameter showed significant difference between right and left eyes (p>0.1 for all comparisons). The male group had larger 24-hour and diurnal IOP fluctuation and MAPE (p<0.05 for all comparisons). Subjects aged 30 or over had higher 24-hour and diurnal mean, higher peak, and larger MAPE (p<0.05 for all comparisons). CONCLUSION: Continuous 24-hour IOP output from the CLS in normal Chinese was stable with a comparable mean level between day and night, as well as scattered acrophase and bathyphase. The 24-hour IOP mean increased with age, and IOP variations were positively correlated to age and male sex.

Expression of the SARS-CoV-2 Receptor ACE2 and Protease TMPRSS2 in Ocular Hypertension Eyes of Nonhuman Primate and Human.

PURPOSE: Coronavirus disease 2019 is a disease caused by the novel severe acute respiratory syndrome coronavirus 2. The double-positive of angiotensin-converting enzyme 2 and transmembrane protease serine type 2 have a higher risk of being infected by severe acute respiratory syndrome coronavirus 2. The susceptibility of coronavirus disease 2019 in patients with chronic diseases, especially in different tissues of ocular hypertension eyes like glaucoma, is not yet known. METHODS: An ocular hypertension model was established by laser photocoagulation in rhesus monkeys. The expression of angiotensin-converting enzyme 2 and transmembrane protease serine type 2 in three ocular hypertension eyes and the three control eyes were analyzed using immunofluorescence. RESULTS: No difference was observed between ocular hypertension and control eyes in the expression of angiotensin-converting enzyme 2 and transmembrane protease serine type 2 in the conjunctival epithelium, corneal epithelium, and ciliary muscle. In ocular hypertension eyes and control eyes, angiotensin-converting enzyme 2 and transmembrane protease serine type 2 expression were both observed in the retina. Angiotensin-converting enzyme 2 staining of retinal ganglion cells was found to be significantly higher in ocular hypertension eyes than in control eyes. However, there was no difference in angiotensin-converting enzyme 2 and transmembrane protease serine type 2 expression in retinal vessels and choroidal vessels between ocular hypertension and control eyes. In our study, the expression and distribution of angiotensin-converting enzyme 2 and TMPREE2 in human retina were similar to that of non-human primates as expected. CONCLUSION: Our study confirmed that angiotensin-converting enzyme 2 and transmembrane protease serine type 2 were expressed widely in rhesus monkey eyes. When compared with controls eyes, the expression of angiotensin-converting enzyme 2 was higher in the retinal ganglion cells in ocular hypertension eyes, suggesting that high ocular pressure may affect the patients' ocular susceptibility to severe acute respiratory syndrome coronavirus 2 infection.

Early impairment of magnocellular visual pathways mediated by isolated-check visual evoked potentials in primary open-angle glaucoma: a cross-sectional study.

OBJECTIVE: To explore different performances in the magnocellular (MC) and parvocellular (PC) visual pathways in patients with primary open-angle glaucoma (POAG) and to objectively assess impairment in early stage of POAG. METHODS AND ANALYSIS: This is a cross-sectional study. MC and PC visual pathways were assessed using isolated-check visual evoked potential (ic-VEP). Visual acuity, intraocular pressure, fundus examination, optical coherence tomography and visual field were measured. Signal-to-noise ratios (SNRs), mediated by ic-VEP were recorded. The Spearman's correlation analysis was used to estimate the relationships between visual functions and structures. Receiver-operating-characteristic (ROC) curves were used to estimate the accuracy in detection of early POAG. RESULTS: 60 participants (30 early POAG eyes and 30 age-matched control subjects) were recruited. MC visual pathway showed a non-linear response function, while PC visual pathway was a linear response function as contrast increased. Early POAG eyes exhibited significantly weaker initial contrast gains and lower maximum responses in the MC visual pathway (p=0.001, p=0.004, respectively). The SNRs at 8% and 32% depths of modulation (DOM) were significantly correlated with temporal-side retinal nerve fibre layer (RNFL) thickness in early POAG in MC-biased stimulation (p=0.017, p=0.020, respectively). The areas under ROC of 16% DOM were 0.780 (sensitivity 80.0%, specificity 63.3%) with the cut-off SNR of 2.07. CONCLUSIONS: The MC visual pathway was damaged in the early stage of POAG. The SNRs at 8% and 32% DOM of MC-biased stimulation were significantly correlated with temporal-side RNFL thickness in early POAG, which helped in understanding the mechanisms of visual impairment in the early stage of POAG.

Reduced interocular suppression after inverse patching in anisometropic amblyopia.

Purpose: Recent investigations observed substantial enhancements in binocular balance, visual acuity, and stereovision among older children and adults with amblyopia by patching the amblyopic eye (i.e., inverse patching) for 2 h daily over 2 months. Despite these promising findings, the precise neural mechanisms underlying inverse patching remain elusive. This study endeavors to delve deeper into the neural alterations induced by inverse patching, focusing on steady-state visual evoked potentials (SSVEPs). We specifically investigate the changes in SSVEPs following monocular deprivation of either the fellow eye or the amblyopic eye in older amblyopic children and adults. Method: Ten participants (17.60 ± 2.03 years old; mean ± SEM), clinically diagnosed with anisometropic amblyopia, were recruited for this study. Each participant underwent a 120 min patching session on their fellow eye on the first day, followed by a similar session on their amblyopic eye on the second day. Baseline steady-state visual evoked potentials (SSVEPs) measurements were collected each day prior to patching, with post-patching SSVEPs measurements obtained immediately after the patching session. The experimental design incorporated a binocular rivalry paradigm, utilizing SSVEPs measurements. Results: The results revealed that inverse patching induced a heightened influence on neural plasticity, manifesting in a reduction of interocular suppression from the fellow eye to the amblyopic eye. In contrast, patching the fellow eye demonstrated negligible effects on the visual cortex. Furthermore, alterations in interocular suppression subsequent to inverse patching exhibited a correlation with the visual acuity of the amblyopic eye. Conclusion: Inverse patching emerges as a promising therapeutic avenue for adolescents and adults grappling with severe anisometropic amblyopia that proves refractory to conventional interventions. This innovative approach exhibits the potential to induce more robust neural plasticity within the visual cortex, thereby modulating neural interactions more effectively than traditional amblyopia treatments.

Long-term surgical outcomes of primary congenital glaucoma in China

OBJECTIVE: To evaluate the long-term outcomes of three surgical procedures for the treatment of primary congenital glaucoma (PCG). INTRODUCTION: PCG is one of the main causes of blindness in children. There is a paucity of contemporary data on PCG in China. METHODS: A retrospective study of 48 patients (81 eyes) with PCG who underwent primary trabeculectomy, trabeculotomy, or combined trabeculotomy and trabeculectomy (CTT). RESULTS: All patients were less than 4 years (yrs) of age, with a mean age of 2.08 ¡À 1.23 yrs. The mean duration of follow-up was 5.49 ¡À 3.09 yrs. The difference in success rates among the three surgical procedures at 1, 3, 6 and 9 yrs was not statistically significant (p = 0.492). However, in patients with over 4 yrs of follow-up, Kaplan-Meier survival analysis revealed that the success rates of trabeculectomy and CTT declined more slowly than that of trabeculotomy. Among the patients, 66.22% acquired good vision (VA ¡Ý 0.4), 17.57% acquired fair vision (VA = 0.1 - 0.3), and 16.22% acquired poor vision (VA < 0.1). The patients with good vision were mostly in the successful surgery group. Myopia was more prevalent postoperatively (p = 0.009). Reductions in the cup-disc ratio and corneal diameter were only seen in the successful surgery group (p = 0.000). In addition, the successful surgery group contained more patients that complied with a regular follow-up routine (p = 0.002). DISCUSSION: Our cases were all primary surgeries. Primary trabeculectomy was performed in many cases because no treatment was sought until an advanced stage of disease had been reached. CONCLUSIONS: In contrast to most reports, in the present study, trabeculectomy and CTT achieved higher long-term success rates than trabeculotomy. The patients with successful surgical results had better vision. Compliance with a routine of regular follow-up may increase the chances of a successful surgical outcome.