An in vivo model for analysis of developmental erythropoiesis and globin gene regulation.

Expression of fetal γ-globin in adulthood ameliorates symptoms of ß-hemoglobinopathies by compensating for the mutant ß-globin. Reactivation of the silenced γ-globin gene is therefore of substantial clinical interest. To study the regulation of γ-globin expression, we created the GG mice, which carry an intact 183-kb human ß-globin locus modified to express enhanced green fluorescent protein (eGFP) from the Gγ-globin promoter. GG embryos express eGFP first in the yolk sac blood islands and then in the aorta-gonad mesonephros and the fetal liver, the sites of normal embryonic hematopoiesis. eGFP expression in erythroid cells peaks at E9.5 and then is rapidly silenced (>95%) and maintained at low levels into adulthood, demonstrating appropriate developmental regulation of the human ß-globin locus. In vitro knockdown of the epigenetic regulator DNA methyltransferase-1 in GG primary erythroid cells increases the proportion of eGFP(+) cells in culture from 41.9 to 74.1%. Furthermore, eGFP fluorescence is induced >3-fold after treatment of erythroid precursors with epigenetic drugs known to induce γ-globin expression, demonstrating the suitability of the Gγ-globin eGFP reporter for evaluation of γ-globin inducers. The GG mouse model is therefore a valuable model system for genetic and pharmacologic studies of the regulation of the ß-globin locus and for discovery of novel therapies for the ß-hemoglobinopathies.

Epidemiology of keratitis/scleritis-related endophthalmitis in a university hospital in Thailand.

To demonstrate the demographics, associated factors, clinical presentations, microbiology, management, visual outcome and complications of keratitis/scleritis-related endophthalmitis (KSE). A retrospective chart of all endophthalmitis patients diagnosed between September 2001 and August 2011 was reviewed. Only endophthalmitis cases with previous corneal or scleral infection were included in the study. The patients were followed until losing vision or eyeball, becoming phthisis, or the end of 2018. Eighty-seven patients with KSE were identified, all unilateral. The mean age was 56.4 ± 21.4 years. There was a slight male predilection (55 patients, 63.2%). The mean follow-up time was 50 ± 149 weeks. The causative pathogens were identified in 35 patients (40.2%), with the highest frequency being bacteria. The most common bacterium was Pseudomonas aeruginosa (n = 13), and the most common fungus was Aspergillus sp. (n = 5). Fifteen patients achieved (17.2%) final visual acuity (VA) of hand motion or better after treatment. Eyeball removal was performed in 61 (70.1%) patients. From multivariate analysis, the only prognostic factor for poor final VA (worse than hand motion, HM) was poor VA (worse than HM) at the initial visit (relative risk 1.97, 95% confidence interval 1.15-3.36, p = 0.013). KSE is uncommon but has a devastating outcome. We found that the patient's initial VA was the only predictor for their final vision. P. aeruginosa was the most common identifiable organism in this study. However, several fungal infections were recognised. These findings should raise awareness for treatment of KSE in the tropics.

Visual outcome of endogenous endophthalmitis in Thailand.

To evaluate a 10-year visual outcome of endogenous endophthalmitis (EE) patients. A 10-year retrospective chart review of EE patients. Thirty-eight patients (40 eyes) were diagnosed with EE at the mean age of 42. Among the identifiable pathogens (71.1% culture positive), the causative agents were predominantly gram-negative bacteria (48.1%). The most common specie was Klebsiella pneumoniae (25.9%). About a quarter of the patients required surgical eye removal, and the remaining 45.7% had visual acuity (VA) worse than hand motion at one month after the infectious episode. The most common complication was ocular hypertension (52.5%). Poor initial VA was significantly associated with a worse visual outcome in the early post-treatment period (p 0.12, adjusted OR 10.20, 95% CI 1.65-62.96). Five patients continued to visit the clinic for at least ten years. One patient had gained his vision from hand motion to 6/7.5. Two patients had visual deterioration, one from corneal decompensation, and the other from chronic retinal re-detachment. Two patients developed phthisis bulbi, with either some VA perception of light or no light perception. Poor initial VA is the only prognostic factor of a poor early post-treatment visual outcome of EE.

Pattern of Contrast Sensitivity Changes in Acute Central Serous Chorioretinopathy.

PURPOSE: To evaluate contrast sensitivity (CS) changes in acute central serous chorioretinopathy (CSC). METHODS: Visual acuity (VA), CS, and subretinal fluid (SRF) were evaluated monthly for 6 months. Treatment was considered at 3 months in case of persistent SRF. RESULTS: Twelve of 20 eyes (60%) had spontaneous SRF resolution within 4 months. Five of 8 patients with delayed SRF resolution received either focal laser or photodynamic therapy. The CS was impaired in all spatial frequencies at baseline. There was a negative correlation between the baseline SRF thickness and CS at 3 and 6 cycles per degree (cpd). The CS improved significantly at the time of fluid resolution (p = 0.001) and continued to improve in 3 and 6 cpd. The CS at 6 cpd did not recover if compared to a normal fellow eye at 6 months (p = 0.018). The CS of 12 cpd at 6 months was superior in the spontaneous resolution group. CONCLUSION: The impaired CS gradually improved as the SRF reduced at all spatial frequencies. CS at 3 and 12 cpd continued to improve after complete fluid resolution. Despite an excellent final VA, the CS at 6 months did not regain its normal value.