Revisiting the role of erythropoietin for treatment of ocular disorders.

Erythropoietin (EPO) is a glycoprotein hormone conventionally thought to be responsible only in producing red blood cells in our body. However, with the discovery of the presence of EPO and EPO receptors in the retinal layers, the EPO seems to have physiological roles in the eye. In this review, we revisit the role of EPO in the eye. We look into the biological role of EPO in the development of the eye and the physiologic roles that it has. Apart from that, we seek to understand the mechanisms and pathways of EPO that contributes to the therapeutic and pathological conditions of the various ocular disorders such as diabetic retinopathy, retinopathy of prematurity, glaucoma, age-related macular degeneration, optic neuritis, and retinal detachment. With these understandings, we discuss the clinical applications of EPO for treatment of ocular disorders, modes of administration, EPO formulations, current clinical trials, and its future directions.

Safety and Efficacy of Human Wharton's Jelly-Derived Mesenchymal Stem Cells Therapy for Retinal Degeneration.

PURPOSE: To investigate the safety and efficacy of subretinal injection of human Wharton's Jelly-derived mesenchymal stem cells (hWJ-MSCs) on retinal structure and function in Royal College of Surgeons (RCS) rats. METHODS: RCS rats were divided into 2 groups: hWJ-MSCs treated group (n = 8) and placebo control group (n = 8). In the treatment group, hWJ-MSCs from healthy donors were injected into the subretinal space in one eye of each rat at day 21. Control group received saline injection of the same volume. Additional 3 animals were injected with nanogold-labelled stem cells for in vivo tracking of cells localisation using a micro-computed tomography (microCT). Retinal function was assessed by electroretinography (ERG) 3 days before the injection and repeated at days 15, 30 and 70 after the injection. Eyes were collected at day 70 for histology, cellular and molecular studies. RESULTS: No retinal tumor formation was detected by histology during the study period. MicroCT scans showed that hWJ-MSCs stayed localised in the eye with no systemic migration. Transmission electron microscopy showed that nanogold-labelled cells were located within the subretinal space. Histology showed preservation of the outer nuclear layer (ONL) in the treated group but not in the control group. However, there were no significant differences in the ERG responses between the groups. Confocal microscopy showed evidence of hWJ-MSCs expressing markers for photoreceptor, Müller cells and bipolar cells. CONCLUSIONS: Subretinal injection of hWJ-MSCs delay the loss of the ONL in RCS rats. hWJ-MSCs appears to be safe and has potential to differentiate into retinal-like cells. The potential of this cell-based therapy for the treatment of retinal dystrophies warrants further studies.

Recalcitrant cystoid macular oedema in an eye with ischaemic central retinal vein occlusion - what's next?

We report a case of a middle-aged gentleman with recalcitrant macular oedema (RMO) secondary to ischaemic central retinal vein occlusion (CRVO). He was given six injections of intravitreal ranibizumab (anti-VEGF) monthly. However, his visual acuity (VA) deteriorated and the macular oedema worsened. He then received an intravitreal dexamethasone implant eight months post-CRVO. His VA and macular oedema improved dramatically and significantly at first follow-up and remained stable at six months after implant. This case can be a reference for those who treating recalcitrant macular oedema. It shows the effect of an intravitreal dexamathasone implant might have in a patient with RMO due to CRVO. The patient enjoyed improvement of vision, with clinical evidence of reduction in central macular thickness (CMT) and with no serious adverse events after a single injection up to six months post implant.

Topical insulin for healing of diabetic epithelial defects?: A retrospective review of corneal debridement during vitreoretinal surgery in Malaysian patients.

PURPOSE: To investigate whether topical insulin improves healing rate of corneal epithelial erosions induced during vitreoretinal surgery in diabetics. METHODS: We retrospectively reviewed case notes and serial post-operative photographs of 15 eyes of 14 patients who had corneal epithelial debridement performed during various vitreoretinal surgeries to improve one surgeon's view over a 10 month period in 2010. RESULTS: Three groups were identified: DTI, comprising diabetics who received topical insulin 1 unit qds postoperatively (n=5); DCT comprising diabetics treated with conventional post-operative medications only (n=5) and NDCT comprising non diabetic patients on conventional post operative therapy (n=5). Only eyes in which the corneal epithelial defect had been serially photographed at time, t= 0, 12, 24, 36, 48, 60, 72 and 120 hours following commencement of topical medications were included. The size of the defect was calculated using local software. DTI eyes had a significantly smaller defect size at t= 24 (p=0.009), 36 (p=0.009), 48 (p=0.015) and 60 hours (p=0.005) compared to DCT eyes and had no statistical difference from NDCT eyes at all times in the Mann Whitney U analysis (p>0.05). In the diabetic operated bilaterally, the insulin treated eye re-epithelialised by 48 hours whereas fellow eye treated conventionally re-epithelialised in 72 hours. CONCLUSIONS: Topical insulin or insulin eye drops 1 unit qds may be applied to the corneal surface to normalize the rate of healing of epithelial defects in diabetic patients undergoing epithelial debridement to improve the surgeon's view.

The Adjunctive Use of Anti-vascular Endothelial Growth Factor Agents in the Management of Iris Neovascularisation in Malaysia.

This retrospective study investigated the role of antivascular endothelial growth factor agents (VEGF), ranibizumab, bevacizumab and pegaptanib sodium in patients with iris neovascularisation (INV), in which 9 eyes received intraocular injections for various ischaemic ocular conditions. Ocular sequelae included recurrence of rubeosis (n=2) and hyphaema (n=2). Systemic complication included one case of cerebrovascular accident. INV regressed in all cases from day one. INV recurrence occurred in 2 cases. The mean intraocular pressure of the study eyes decreased from 25.3 mmHg to 18.3 mmHg at one month. Five eyes are medication free. Visual acuity improved in 5 eyes. Four eyes achieved a Snellen visual acuity of 6/24 or better. We conclude that the use of intraocular anti-VEGF agents are safe and effective for inducing the regression of INV. Patients with multiple systemic risk factors should be counseled on stroke risk.

Bilateral corneal perforation in a sexually active adult male with gonococcal conjunctivitis.

A 41 year-old Malay man had been treated by general practitioners for bilateral red eyes with profuse discharge of three weeks' duration with no improvement. He then presented to an ophthalmologist who noted profuse purulent discharge, bilateral corneal perforation, lid swelling and chemosis. Culture of the ocular discharge grew Neisseria gonorrhoeae. Treatment with systemic and topical antibiotics prevented microperforations in the right eye from progressing to overt perforation and was able to control disease in the left eye.

Accelerated diabetic retinopathy in pregnancy--a real and present danger.

A 36 year-old Malay lady with diabetes mellitus in pregnancy and poorly controlled hypertension developed rapid progression of diabetic retinopathy from no retinopathy to florid proliferative retinopathy over three months in her right eye. She had subsequent loss of vision due to vitreous haemorrhage in the peri-partum period. She had good final visual acuity with quiescent retinopathy following pars planar vitrectomy. A similar course was avoided in the left eye by timely pan retinal photocoagulation.

Multifocal choroiditis: ocular TB or side-effects of anti-TB therapy?

A patient with end-stage renal failure secondary to polycystic kidney disease was seen in the Eye Clinic for a corneal abrasion. Incidental fundal examination revealed bilateral multiple, small, raised, pale yellow sub-retinal nodules. Past medical history of inadequately treated pulmonary tuberculosis was obtained. Following initiation of anti-tuberculous therapy, the choroidal lesions resolved.