Pharmacogenetic Influence of LOC387715/HTRA1 on the Efficacy of Bevacizumab Treatment for Age-Related Macular Degeneration in a Korean Population

PURPOSE: The purpose of this study was to determine the pharmacogenetic effects of complement factor H (CFH) Y402H, LOC387715 and high-temperature requirement factor A1 (HTRA1) genotypes on the treatment of exudative age-related macular degeneration (AMD) by intravitreal bevacizumab injection in a Korean population. METHODS: Seventy-five patients diagnosed with exudative AMD were treated with intravitreal bevacizumab (2.5 mg) monotherapy. All patients received three initial intravitreal bevacizumab injections every four weeks and were then treated "as needed" based on clinical findings, optical coherence tomography and fluorescein angiography during the 12 month follow-up period after the third injection. RESULTS: The difference in visual acuity improvement among the three genotypes of LOC387715 were statistically significant at six months post-treatment (logarithm of the minimum angle of resolution; TT, 0.346; GT, 0.264; GG, 0.188; p = 0.037). Among the LOC387715 genotypes, the number of additional injections was lower in patients who had the risk T allele (GG, 2.143; GT, 2.000; TT, 1.575; p = 0.064). There was no significant difference between visual acuity and central macular thickness change in the CFH Y402H polymorphism group during the 12 month follow-up period. However, the TC group of CFH Y402H required more additional bevacizumab injections than the TT group (TT, 1.517; TC, 3.363; p = 0.020). CONCLUSIONS: This study demonstrated that different LOC387715/HTRA1 genotypes resulted in different bevacizumab treatment responses on exudative AMD. Patients with the risk allele had an improved treatment response and less need for additional injections. However, patients with the CFH Y402H risk allele needed more additional injections of bevacizumab in order to improve visual acuity. This study illustrates how pharmacogenetic factors may help determine treatment modality and dosing. This could ultimately provide basic data for 'personalized medicine' in AMD.

The Antifibrotic Effects of alpha-Tocotrienols in Primary Cultured Orbital Fibroblasts from Thyroid-Associated Ophthalmopathy Patients

PURPOSE: To evaluate the antiproliferative and antifibrotic effects of alpha-tocotrienols in primary cultured orbital fibroblasts from thyroid-associated ophthalmopathy (TAO) patients. METHODS: Orbital fibroblasts were cultured (5 eyes from TAO patients, 5 eyes from normal patients) and classified into a control group, alpha-tocotrienol group and alpha-tocopherol group. The cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The proliferation of orbital fibroblasts was measured using the Click-iT(TM) assay. The collagen production of the control and alpha-tocotrienol groups was measured using a hydroxyproline assay. RESULTS: The alpha-tocotrienol and alpha-tocopherol groups showed no cytotoxicity up to 150 microm in orbital fibroblasts from TAO and normal patients. The proliferation of orbital fibroblasts from TAO and normal patients was significantly inhibited with alpha-tocotrienol at 80 microm and 120 microm. The collagen production of orbital fibroblasts from TAO patients was significantly inhibited with alpha-tocotrienol at 120 microm. CONCLUSIONS: The results from the present study indicate that non-toxic concentrations of alpha-tocotrienol have significant antiproliferative and antifibrotic effects on orbital fibroblasts from TAO patients.

Complications after Intravitreal Triamcinolone Acetonide Injection: Incidence and Risk Factors

PURPOSE: To reduce complications and provide proper management for better clinical outcomes in the treatment of macular edema through a large-scale analysis of the incidence and risk factors for complications of intravitreal triamcinolone injection. METHODS: The medical records of 490 eyes that received intravitreal triamcinolone (4.0 mg) injection for treatment of macular edema caused by various diseases were retrospectively reviewed, and relevant parameters were included in a multivariate regression model. RESULTS: Vitrectomized (p < 0.001) and pseudophakic (p = 0.054) eyes were less likely to exhibit an intraocular pressure increase, but glaucoma (p < 0.001) and young age (p = 0.073) were found to be significant risk factors for this complication. Vitrectomized eyes (p = 0.011), diabetic macular edema (p < 0.001), secondary ocular hypertension (p = 0.029) and old age (p = 0.059) were associated with cataract progression. Three consecutive case of sterile endophthalmitis, which differs from bacterial endophthalmitis in clinical course and prognosis, occurred during the same period. CONCLUSIONS: Risk factors and the incidence of complications after intravitreal triamcinolone injection should be evaluated through regular follow-up evaluation to ensure proper management and a better prognosis.

Two Different Cases of Stenotrophomonas Maltophilia Endophthalmitis after Cataract Surgery

PURPOSE: To report 2 different cases of postoperative endophthalmitis caused by Stenotrophomonas maltophilia after cataract surgery. CASE SUMMARY: A 73-year-old male with diabetes mellitus developed severe pain in the right eye 2 weeks after cataract surgery. The patient was hospitalized with a diagnosis of infectious endophthalmitis, and vitrectomy was performed. Cultures of aqueous humor and vitreous aspirate revealed S. maltophilia. On day 30 after vitrectomy, his visual acuity had improved to 20/20 and there were no recurrences. A 61-year-old female with no significant past medical history was referred for uveitis or delayed onset endophthalmitis 30 days after cataract surgery. An anterior chamber tapping and cultures were performed. S. maltophilia and Aspergillus fumigatus were isolated. The patient received antibiotics and antifungal agents and her visual acuity improved to 20/25. CONCLUSIONS: S. maltophilia has been considered a life-threatening systemic opportunistic infection; however, the organism has recently been reported as an exogenous pathogen of endophthalmitis following cataract surgery. Herein, 2 different cases of S. maltophilia endophthalmitis after cataract surgery are presented and compared with previous case reports.

Three Various Cases of Retinal Hemorrhages Caused by Plasmodium vivax Malaria

PURPOSE: To report three various cases of retinal hemorrhages caused by Plasmodium vivax malaria. CASE SUMMARY: Two 55-year-old male patients and a 52-year-old male patient with cyclic high fever were admitted to the department of internal medicine. Three of the patients were diagnosed with malaria caused by P. vivax based on a peripheral blood smear. The patients were treated with hydroxychloroquine and premaquine but complained of decreased visual acuity. The patients were examined with funduscopy, fluorescein angiography, and optical coherence tomography. The first case showed 2 areas of retinal hemorrhages on the macular in the right eye and 1 area of retinal hemorrhage in the left eye. The second case showed many cotton-wool spots along with a number of small retinal hemorrhages and tortuous blood vessels in both eyes. The third case showed 1 area of retinal hemorrhage in the right eye and many cotton-wool spots in both eyes. CONCLUSIONS: P. vivax malaria rarely causes retinal hemorrhage. Manifestations of retinal hemorrhage and degree of visual acuity loss may vary among patients. P. vivax malaria should be considered when patients with unexplained high fever present with retinal hemorrhage, even without a history of overseas travel.