SOX2 Regulates P63 and Stem/Progenitor Cell State in the Corneal Epithelium.

Mutations in key transcription factors SOX2 and P63 were linked with developmental defects and postnatal abnormalities such as corneal opacification, neovascularization, and blindness. The latter phenotypes suggest that SOX2 and P63 may be involved in corneal epithelial regeneration. Although P63 has been shown to be a key regulator of limbal stem cells, the expression pattern and function of SOX2 in the adult cornea remained unclear. Here, we show that SOX2 regulates P63 to control corneal epithelial stem/progenitor cell function. SOX2 and P63 were co-expressed in the stem/progenitor cell compartments of the murine cornea in vivo and in undifferentiated human limbal epithelial stem/progenitor cells in vitro. In line, a new consensus site that allows SOX2-mediated regulation of P63 enhancer was identified while repression of SOX2 reduced P63 expression, suggesting that SOX2 is upstream to P63. Importantly, knockdown of SOX2 significantly attenuated cell proliferation, long-term colony-forming potential of stem/progenitor cells, and induced robust cell differentiation. However, this effect was reverted by forced expression of P63, suggesting that SOX2 acts, at least in part, through P63. Finally, miR-450b was identified as a direct repressor of SOX2 that was required for SOX2/P63 downregulation and cell differentiation. Altogether, we propose that SOX2/P63 pathway is an essential regulator of corneal stem/progenitor cells while mutations in SOX2 or P63 may disrupt epithelial regeneration, leading to loss of corneal transparency and blindness. Stem Cells 2019;37:417-429.

TOPICAL APRACLONIDINE REDUCES PAIN AFTER INTRAVITREAL INJECTIONS: A Double-Blind Randomized Controlled Trial.

PURPOSE: To evaluate the efficacy of topical apraclonidine in reducing pain and subconjunctival hemorrhage (SCH) after intravitreal injections (IViT). METHODS: A prospective, randomized, double-blinded study. Thirty-nine patients were examined twice, at each monthly IViT of 1.25 mg/0.05 mL bevacizumab. Patients were randomly assigned to receive either topical apraclonidine 0.5% or placebo to the treated eye, 30 minutes before the first IViT. At their second IViT, the intervention was switched. Thirty minutes after the injection, SCH size was measured by a slit lamp, and pain was assessed by the numerical rating scale (NRS-11). RESULTS: Mean pain score was 1.69 (SD ±1.44) in the apraclonidine group and 3.28 (SD ±2.27) in the control group (P < 0.001). Phakic patients had a greater pain reduction after topical apraclonidine (P < 0.001). Subconjunctival hemorrhage incidence was 41% in the apraclonidine group and 51.3% in the control group (P = 0.503). Mean SCH size was 1.71 mm (SD ±5.83) in the apraclonidine group and 3.25 mm (SD ±6.41) in the control group (P = 0.253). After topical apraclonidine, there was a smaller reduction in SCH size in patients with choroidal neovascularization or hypertension (P = 0.003 and 0.044, respectively), and a greater reduction in phakic patients (P = 0.048). CONCLUSION: Topical apraclonidine 0.5%, administered 30 minutes before IViT, significantly decreased pain by a factor of 1.94. It did not decrease the incidence or size of SCH in the entire cohort, but only in several subpopulations.

The impact of Ramadan fast on patients with gout.

BACKGROUNDS: Ramadan fast is a religious custom in Islam. Increased serum uric acid level during this month had been reported in past studies of nongout patients. OBJECTIVES: The objective of this study was to assess the impact of Ramadan fast on patients with gout. METHODS: All Moslem patients with gout from the registry of Nazareth Hospital, who intended to fast during Ramadan, were asked to participate in our study (group 1). Data regarding age, gender, income, education, duration of gout, meds, adherence to low-purine diet, and gouty attacks were documented. Age- and gender matched Moslem patients from the same registry, but who did not intend to fast during Ramadan, were asked to participate as a control group (group 2). Just prior to and at the end of Ramadan, blood for uric acid, creatinine, and urea levels were obtained as well as body mass index, from all the patients. During Ramadan, patients were monitored for gouty arthritis or renal calculi attacks, as well as low-purine diet and medicine adherence. RESULTS: Twenty-one and 22 patients from groups 1 and 2, respectively, completed the study. Mean serum uric acid, urea, creatinine, and body mass index levels at the end of Ramadan fasts in group 1 patients were 8.11 mg/dL, 26.38 mmol/L, 0.87 mg/dL, and 31.0 kg/m, respectively, as compared with 7.92 mg/dL (P = 0.707), 24.54 mmol/L (P = 0.769), 0.84 mg/dL (P = 0.180), and 30.5 kg/m (P = 0.907) respectively, obtained just prior to the fast. No significant change in any parameter was seen also in group 2 patients. There also was no significant change between the 2 groups in arthritis or renal calculi attacks and also in medication and low-purine diet adherence, during Ramadan. CONCLUSIONS: There was no risk for a significant increase in gouty arthritic/renal calculi attacks or serum uric acid in patients with gout during Ramadan fast.

Peripapillary Atrophy Area as an Indicator of Glaucomatous Structural and Functional Progression.

Purpose: To determine whether peripapillary atrophy (PPA) area is an indicator of glaucomatous structural and functional damage and progression. Methods: In this retrospective longitudinal analysis from ongoing prospective study we qualified 71 eyes (50 subjects) with glaucoma. All subjects had a comprehensive ophthalmic examination, visual field (VF), and spectral-domain optical coherence tomography (OCT) testing in at least three visits. PPA was manually delineated on en face OCT optic nerve head scans, while observing the corresponding cross-sectional images, as the hyper-reflective area contiguous with the optic disc. Results: The mean follow-up duration was 4.4 ± 1.4 years with an average of 6.8 ± 2.2 visits. At baseline, PPA area was significantly associated only with VF's mean deviation (MD; P = 0.041), visual field index (VFI; P = 0.041), superior ganglion cell inner plexiform layer (GCIPL; P = 0.011), and disc area (P = 0.011). Longitudinally, PPA area was negatively and significantly associated with MD (P = 0.015), VFI (P = 0.035), GCIPL (P = 0.009), superior GCIPL (P = 0.034), and disc area (P = 0.007, positive association). Conclusions: Longitudinal change in PPA area is an indicator of glaucomatous structural and functional progression but PPA area at baseline cannot predict future progression. Translational Relevance: Longitudinal changes in peripapillary atrophy area measured by OCT can be an indicator of structural and functional glaucoma progression.

Corneal Perforation after Nd: YAG Capsulotomy: A Case Report and Literature Review.

BACKGROUND: Nd: YAG capsulotomy is the treatment of choice for posterior capsular opacification after cataract surgery. We report a case of corneal perforation following Nd:YAG capsulotomy in a patient with systemic scleroderma. CASE PRESENTATION: A 69-year-old woman presented with acute onset of blurred vision 2 weeks following Nd:YAG laser capsulotomy for posterior subcapsular opacification. On examination, her best-corrected visual acuity was 1/120, and bio-microscopy revealed a central full-thickness corneal laceration. Conservative treatment consisted of topical ocular antibiotics, cycloplegics, hypotensive drops and a soft therapeutic contact lens. Her final visual acuity improved to 6/18 with resolution of the corneal laceration. CONCLUSION: The possibility of corneal perforation after Nd-YAG capsulotomy in patients with systemic scleroderma and connective tissue disease should be borne in mind when treating such patients.