Differential protection of injured retinal ganglion cell dendrites by brimonidine.

PURPOSE: To determine whether brimonidine protects against the retraction and loss of retinal ganglion cell (RGC) dendrites after optic nerve crush (ONC). METHODS: Fluorescent RGCs of mice expressing yellow fluorescent protein (YFP) under the control of the Thy-1 promoter (Thy1-YFP mice) were imaged in vivo and assigned to one of six groups according to dendrite structure. The mice then received brimonidine every other day starting 2 days before, or 2 or 6 days after, unilateral ONC. Control animals received vehicle every other day starting 2 days before ONC. Control animals received vehicle every other day starting 2 days before ONC. Total dendrite length, dendrite branching complexity, and the time until complete loss of dendrites were assessed weekly for 4 weeks. RESULTS: Overall, brimonidine treatment significantly slowed the complete loss of RGC dendrites and significantly slowed the reduction of total dendrite length and branching complexity. Separate analysis of each RGC group showed brimonidine significantly delayed the time until complete loss of dendrites in four of the RGC groups. These delays generally were similar when treatment started either 2 days before or 2 days after ONC, but were smaller or absent when treatment started 6 days after ONC Protection against loss of total dendrite length and loss of branching complexity was observed in three of the RGC groups. In two of these RGC groups, protective effects persisted until the end of the study. CONCLUSIONS: Brimonidine protects many RGC types against dendrite retraction, loss of branching complexity, and complete loss of dendrites following ONC. However, the pattern and magnitude of this protection differs substantially among different RGC types. These results indicate that requirements for RGC-protective therapies following optic nerve injury may differ among RGC types.

Brimonidine protects against loss of Thy-1 promoter activation following optic nerve crush.

BACKGROUND: The loss of RGCs expressing Thy-1 after optic nerve injury has an initial phase of rapid decline followed by a longer phase with slower reduction rate. This study used longitudinal retinal imaging of mice expressing cyan fluorescent protein under control of the Thy-1 promoter (Thy1-CFP mice) to determine how the α2-adrenergic agonist brimonidine influences loss of Thy1 promoter activation. METHODS: Baseline images of the fluorescent retinal neurons in 30 Thy1-CFP mice were obtained using a modified confocal scanning laser ophthalmoscope. Next, brimonidine (100 ug/kg, IP) was administered either one time immediately after optic nerve crush, or immediately after optic nerve crush and then every 2 days for four weeks. A control group received a single saline injection immediately after optic nerve crush. All animals were imaged weekly for four weeks after optic nerve crush. Loss of fluorescent retinal neurons within specific retinal areas was determined by counting. RESULTS: At one week after optic nerve crush, the proportion of fluorescent retinal neurons retaining fluorescence was 44±7% of baseline in control mice, 51±6% after one brimonidine treatment, and 55±6% after brimonidine treatment every other day (P<0.05 for both brimonidine treatment groups compared to the control group). Subsequently, the number of fluorescent retinal neurons in the group that received one treatment differed insignificantly from the control group. In contrast, the number of fluorescent retinal neurons in the group that received repeated brimonidine treatments was greater than the control group by 28% at two weeks after crush and by 32% at three weeks after crush (P<0.05 at both time points). Rate analysis showed that brimonidine slowed the initial rate of fluorescent cell decline in the animals that received multiple treatments (P<0.05). Differences in the rate of loss among the treatment groups were insignificant after the second week. CONCLUSION: Repeated brimonidine treatments protect against loss of fluorescence within fluorescent retinal neurons of Thy1-CFP mice after optic nerve crush. As most of fluorescent retinal neurons in this system are RGCs, these findings indicate that repeated brimonidine treatments may protect RGC health following optic nerve crush.

Inhibition of histone deacetylases 1 and 3 protects injured retinal ganglion cells.

PURPOSE: Thy-1 is a marker of retinal ganglion cell (RGC) differentiation. Optic nerve injury triggers reduction of Thy-1 promoter activation followed by retinal ganglion cell (RGC) death. This study determined whether MS-275, an inhibitor of the histone deacetylases 1 and 3, can inhibit these changes. METHODS: Mice expressing cyan fluorescent protein (CFP) under control of the Thy-1 promoter received MS-275 (subcutaneous) or vehicle three times per week starting 1 week before optic nerve crush and continuing for 6 weeks. The same retinal area was imaged using the blue-light confocal scanning laser ophthalmoscope before and after optic nerve crush every week, and fluorescent spots were counted manually. The eyes were then processed for histopathologic analysis. RESULTS: The mean proportions of fluorescent retinal neurons remaining in the vehicle group following optic nerve crush were 36 ± 8, 18 ± 6, 13 ± 10, 12 ± 4, 13 ± 5, and 13 ± 5% at weeks 1 through 6, respectively (n = 6). In contrast, the mean proportions of fluorescent retinal neurons remaining in the group treated with MS-275 were 59 ± 19, 39 ± 11, 34 ± 12, 33 ± 15, 32 ± 13, and 27 ± 15% at weeks 1 through 6, respectively (n = 7, P < 0.05 at weeks 1 through 5). Rate analysis showed that MS-275 slowed the rate of loss during the first 2 weeks by 23% (P < 0.05) and subsequently was similar. Histopathologic analysis revealed 27 ± 13% greater ganglion cell layer (GCL) neurons in the eyes from mice that received MS-275 treatment (P < 0.02). CONCLUSIONS: These results indicate that treatment with MS-275 protects against the loss of RGC differentiation and promotes RGC survival following optic nerve injury.

The surgical outcome of primary trabeculectomy with mitomycin C and A fornix-based conjunctival flap technique in Thailand.

OBJECTIVE: To determine the surgical outcome of primary trabeculectomy with mitomycin C (MMC) and fornix-based conjunctival flap technique in Thai patients. MATERIAL AND METHOD: This retrospective review was conducted from the clinical records of all Thai glaucoma patients who underwent a primary trabeculectomy with MMC using a fornix-based conjunctival flap technique by or under supervision of one ophthalmologist (NK) between February 2004 and July 2006 at Siriraj Hospital, School of Medicine, Mahidol University, Bangkok, Thailand. RESULTS: There were 69 eyes from 60 patients. Postoperatively, mean intraocular pressure (IOP) was significantly decreased from 26.1 +/- 11.7 mmHg to 11.7 +/- 4.4 mmHg (p < 0.001) and mean number of anti-glaucoma medication was significantly reduced from 3.9 +/- 0.7 to 0.3 +/- 0.9 (p < 0.001) at last visit. Sixty-seven eyes (96.8%) were considered as success. Eight eyes (11.6%) in this group needed topical anti-glaucoma medications. Two eyes (2.9%) were considered as failure. Mean follow-up period was 7.7 +/- 4.0 months. Complications included bleb leaking in 16 eyes, choroidal detachment in four eyes, and blebitis in two eyes. Seven eyes with leaking bleb resolved spontaneously. CONCLUSION: Primary trabeculectomy with MMC using afornix-based conjunctival flap technique is effective as a treatment for Thai glaucoma patients. There is a high rate of success (96.8%) with the low rate of complication.

Surgical outcome of intravitreal bevacizumab and filtration surgery in neovascular glaucoma.

INTRODUCTION: The purpose of this study was to evaluate the surgical outcome of a trabeculectomy with mitomycin C (MMC) in neovascular glaucoma after an adjunctive treatment with intravitreal bevacizumab (Avastin(R); Genentech Inc, San Francisco, CA, USA) injection (IVB). METHODS: Six patients with NVG presented at the Department of Ophthalmology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Thailand. After adequate panretinal photocoagulation (PRP) and maximal antiglaucoma medication therapy, these patients received IVB (1.25 mg in 0.05 ml) due to persistent neovascularisation of the iris (NVI). A fornix-based conjunctival flap trabeculectomy with MMC was performed within 4 weeks following administration of IVB. RESULTS: Three patients with proliferative diabetic retinopathy (PDR) and three patients with central retinal vein occlusion (CRVO) were enrolled in the study (mean age, 57 years). Absolute regression of NVI was observed within 1 week after IVB in four patients. In two patients NVI was reduced but still persisted. Mean intraocular pressure (IOP) decreased from 39.8 mmHg pre-operatively to 7.5 mmHg on the first postoperative day. No intra-operative complications were noted. Two patients had postoperative hyphema, which resolved spontaneously within 1 week. During the mean follow up of 24.7 weeks, five patients had controlled IOP (range, 2-16 mmHg) without antiglaucoma medication. Two patients with PDR had improved visual acuity whereas two patients with CRVO lost pre-operative light perception. Recurrent NVI was subsequently detected in one patient who had uncontrolled IOP. This patient underwent transscleral diode laser cyclophotocoagulation and additional PRP. All patients were symptom-free at last visit. CONCLUSION: IVB is an effective modality to reduce intra-operative complications during trabeculectomy for neovascular glaucoma. The short-term outcomes following trabeculectomy with MMC are favourable.

Eyelid tumors in Siriraj Hospital from 2000-2004.

OBJECTIVES: To determine the relative incidence of eyelid lesions seen in Siriraj Hospital from January 2000-April 2004. STUDY DESIGN: Retrospective charts review MATERIAL AND METHOD: Two hundred and ninety-seven cases of eyelid lesions seen in Siriraj Hospital from 2000 to 2004 were analyzed. RESULTS: There were 53 (17.8%) inflammatory conditions, 212 (71.4%) benign eyelid tumors and 32 (10.8%) malignant eyelid tumors. These 32 malignant eyelid tumors included 13 sebaceous gland carcinomas, 12 basal cell carcinomas, 3 malignant melanomas, 2 squamous cell carcinomas, 1 apocrine adenocarcinoma and 1 metastatic carcinoma. Various flaps techniques or primary closures were used for reconstruction in 20 cases. Six cases needed exenteration. CONCLUSION: The majority of eyelid lesions were benign eyelid tumors while malignant eyelid tumors contributed 10.8% of the total eyelid lesions. Sebaceous gland carcinoma was the most common eyelid tumor found in their present study that was consistent with other studies from Asian countries.