Comparative ophthalmic assessment of patients receiving tafenoquine or chloroquine/primaquine in a randomized clinical trial for Plasmodium vivax malaria radical cure.

PURPOSE: Ophthalmic safety observations are reported from a clinical trial comparing tafenoquine (TQ) efficacy and safety versus sequential chloroquine (CQ)/primaquine (PQ) for acute Plasmodium vivax malaria. METHODS: In an active-control, double-blind study, 70 adult subjects with microscopically confirmed P. vivax malaria were randomized (2:1) to receive 400 mg TQ × 3 days or 1500 mg CQ × 3 days then 15 mg PQ × 14 days. MAIN OUTCOME MEASURES: clinically relevant changes at Day 28 and Day 90 versus baseline in the ocular examination, color vision evaluation, and corneal and retinal digital photography. RESULTS: Post-baseline keratopathy occurred in 14/44 (31.8%) patients with TQ and 0/24 with CQ/PQ (P = 0.002). Mild post-baseline retinal findings were reported in 10/44 (22.7%) patients receiving TQ and 2/24 (8.3%) receiving CQ/PQ (P = 0.15; treatment difference 14.4%, 95% CI - 5.7, 30.8). Masked evaluation of retinal photographs identified a retinal hemorrhage in one TQ patient (Day 90) and a slight increase in atrophy from baseline in one TQ and one CQ/PQ patient. Visual field sensitivity (Humphrey™ 10-2 test) was decreased in 7/44 (15.9%) patients receiving TQ and 3/24 (12.5%) receiving CQ/PQ; all cases were < 5 dB. There were no clinically relevant changes in visual acuity or macular function tests. CONCLUSIONS: There was no evidence of clinically relevant ocular toxicity with either treatment. Mild keratopathy was observed with TQ, without conclusive evidence of early retinal changes. Eye safety monitoring continues in therapeutic studies of low-dose tafenoquine (300 mg single dose). CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01290601.

A randomized, double-blind, active-control trial to evaluate the efficacy and safety of a three day course of tafenoquine monotherapy for the treatment of Plasmodium vivax malaria.

BACKGROUND: Tafenoquine is an investigational 8-aminoquinoline for the prevention of Plasmodium vivax relapse. Tafenoquine has a long half-life and the potential for more convenient dosing, compared with the currently recommended 14-day primaquine regimen. METHODS: This randomized, active-control, double-blind trial was conducted in Bangkok, Thailand. Seventy patients with microscopically confirmed P. vivax were randomized (2:1) to tafenoquine 400 mg once daily for 3 days or 2500 mg total dose chloroquine phosphate (1500 mg chloroquine base) given over 3 days plus primaquine 15 mg daily for 14 days. Patients were followed to day 120. RESULTS: Day 28 adequate clinical response rate in the per-protocol population was 93% (40/43) (90%CI 83-98%) with tafenoquine, and 100% (22/22) (90%CI 87-100%) with chloroquine/primaquine. Day 120 relapse prevention was 100% (35/35) with tafenoquine (90%CI 92-100%), and 95% (19/20) (90%CI 78-100%) with chloroquine/primaquine. Mean (SD) parasite, gametocyte and fever clearance times with tafenoquine were 82.5 h (32.3), 49.1 h (33.0), and 41.1 h (31.4) versus 40.0 h (15.7), 22.7 h (16.4), and 24.7 h (17.7) with chloroquine/primaquine, respectively. Peak methemoglobin was 1.4-25.6% (median 7.4%, mean 9.1%) in the tafenoquine arm, and 0.5-5.9% (median 1.5%, mean 1.9%) in the chloroquine/primaquine arm. There were no clinical symptoms of methemoglobinemia in any patient. DISCUSSION: Although there was no difference in efficacy in this study, the slow rate of parasite, gametocyte and fever clearance indicates that tafenoquine should not be used as monotherapy for radical cure of P. vivax malaria. Also, monotherapy increases the potential risk of resistance developing to this long-acting agent. Clinical trials of single-dose tafenoquine 300 mg combined with standard 3-day chloroquine or artemisinin-based combination therapy are ongoing. TRIAL REGISTRATION: Clinicaltrials.gov NCT01290601.

Long-term intraocular pressure change after clear corneal phacoemulsification in Thai glaucoma patients.

OBJECTIVES: To evaluate long-term intraocular pressure (IOP) changes after sutureless clear corneal phacoemulsification in eyes with preoperatively controlled glaucoma. DESIGN: Retrospective study. SETTING: Eye Clinic, Ramathibodi Hospital, Faculty of Medicine, Mahidol University. MATERIAL AND METHOD: The medical records of 218 patients who had uneventful sutureless clear corneal phacoemulsification with acrylic foldable lens (IOL) implantation were retrospectively reviewed. Included were 58 patients with medically controlled open-angle glaucoma and 160 normal controls. Follow-up was 12 to 18 months. Outcome measures were postoperative IOP and number of glaucoma medications. RESULTS: Postoperatively, there was an insignificant decrease in IOP in the glaucoma group; the mean decrease was 1.4 mm Hg +/- 3.8 (SD) at 12 months and 1.6 +/- 4.2 mm Hg at 18 months. The mean number of medications decreased significantly at 12 months (0.51 +/- 0.75) and at 18 months (0.41 +/- 0.83) (P = .04). The control group also had a significant decrease in IOP, with a mean decrease of 0.83 +/- 2.8 mm Hg at 12 months (P = .01) and 1.26 +/- 2.9 mm Hg at 18 months (P < .0001). The decrease in IOP was more pronounced in eyes with a higher preoperative IOP in both the glaucoma and control groups. CONCLUSION: These findings suggest that sutureless clear corneal phacoemulsification with foldable acrylic IOL implantation is a relatively safe and simple surgical option in patients with cataract and well-controlled glaucoma. The approach provided favorable long-term IOP change and led to rapid visual rehabilitation in both the glaucoma and control group.

The efficacy of unoprostone isopropyl as an adjunct to topical beta-blocker in patients with open angle glaucoma: a-6-month study.

OBJECTIVES: To assess the efficacy and safety of unoprostone isopropyl as an adjunctive treatment to topical beta-blocker in patients with primary open angle glaucoma (POAG). STUDY DESIGN: This was a prospective, open-label clinical study. MATERIAL AND METHOD: A total of 44 eyes of 22 eligible patients whose intraocular pressure (IOP) was inadequately controlled by topical beta-blocker were enrolled. Inclusion criteria consisted of patients with primary open angle glaucoma who either had IOP measurements > or = 22 mmHg while on topical beta-blocker monotherapy or had IOP measurements > or = 18 mmHg while on dual therapy (topical beta-blocker and a second drug of a different class which was to be discontinued prior to the study to allow washing out of its effects). INTERVENTION: Baseline IOP, pupil size, blood pressure and pulse rate were initially measured; the patients were then examined at 2nd, 4th, 8th, 12th, 18th and 24th weeks of following commencement of topical unoprostone isopropyl therapy (given twice daily). MAIN OUTCOME MEASURES: IOP pupil size, blood pressure and pulse rate were measured and were compared to baseline values. RESULTS: In 44 eyes of 22 eligible patients, unoprostone isopropyl resulted in a statistically significant IOP reduction of 24.6% (p < 0.02). The mean systolic blood pressure decreased from 132.79 +/- 22.11 mmHg (range 100-180 mmHg) at baseline to 125.77 +/- 18.40 mmHg (range 80-160 mmHg) at 24th week after unoprostone isopropyl administration. This reduction was statistically significant (p = 0.002) but was unlikely to have clinical importance. Both mean diastolic blood pressure (p = 0.344), pulse rate (p = 0.306), and pupil diameter (p = 0.107) were not significantly affected. CONCLUSION: Topical unoprostone isopropyl beneficially provides additive IOP lowering effect to topical beta-blocker in patients with primary open angle glaucoma. No serious systemic side effects were found in the present study.

Intraocular pressure control following phacoemulsification in patients with chronic angle closure glaucoma.

OBJECTIVES: To evaluate intraocular pressure (IOP) and glaucoma control following phacoemulsification with posterior chamber intraocular lens implantation in patients who had chronic angle closure glaucoma (CACG) whose peripheral anterior synechiae (PAS) were less than 270 degrees. DESIGN: Non-randomized consecutive cases series. PARTICIPANTS: CACG cases at the glaucoma service, Ramathibodi Hospital who underwent Neodymium YAG laser peripheral iridotomy (PI) and subsequently received or did not receive anti-glaucoma medication. MATERIAL AND METHOD: Retrospective analysis of CACG patients who had PAS 270 degrees or less and underwent YAG-PI with or without anti-glaucoma medication to control IOP at 21 mmHg or less. The IOP and number of anti-glaucoma medication used at 1, 3 and 6 months were measured. Patients were classified into 2 Groups according to degree of PAS: Group 1 were patients who had PAS 180 degrees or less and Group 2 were those whose PAS was between 181 degrees and 270 degrees. MAIN OUTCOME MEASURES: The IOP and number of anti-glaucoma medication at baseline and postoperatively at 1, 3 and 6 months were compared by nonparametric statistics. RESULTS: There were 28 patients (48 eyes) in the present study. Twenty two were females and 6 were males. Patients' age ranged from 45 to 76 years old with a mean of 55 +/- 6.5 years. Of the 48 eyes, 34 were in Group 1 and 14 were in Group 2. In Group 1, the mean baseline IOP was 20 +/- 2.5 mmHg. and the average number of preoperative anti-glaucoma medication used was 0.08. At 1, 3 and 6 months postoperatively, the IOPs were 16.2 +/- 2.2, 17.1 +/- 2.0, 18.1 +/- 1.4 mmHg. respectively with an average number of anti-glaucoma medications of 0, 0.3 and 0.3, respectively, whereas in Group 2, the mean baseline IOP was 22 +/- 3.8 mmHg and mean preoperative number of anti-glaucoma was 1.8, whereas postoperatively, the IOPs at 1, 3 and 6 months were 17.1 +/- 2.2, 17.3 +/- 1.8, and 17.1 +/- 1.7 mmHg, with an average number of 1.1, 1.4 and 1.4 anti-glaucoma medications used, respectively. When compared between the 2 Groups, Group 1 had a significant difference in IOP control at 1 and 3 months and less use of antiglaucoma medications than Group 2 up to at least 6 months. CONCLUSION: Phacoemulsification in CACG helped control of glaucoma. There was a statistically significant difference in IOP reduction and number of anti-glaucoma medication used before and after phacoemulsification in the CACG patients whose PAS did not exceed 270 degrees at least up to 6 months.

Long-term results of early trabeculectomy with mitomycin-C and subsequent posterior segment intervention in the treatment of neovascular glaucoma with hazy ocular media.

OBJECTIVES: To assess the long-term efficacy and safety of early trabeculectomy with mitomycin-C (TMMC) and subsequent posterior segment intervention in the treatment of neovascular glaucoma (NVG) with hazy ocular media. MATERIAL AND METHOD: Twenty-three eyes of 21 patients who had NVG with hazy ocular media that precluded posterior segment and had persistent IOP of 30 mm Hg or more despitefully antiglaucoma medications for 48 hours, underwent a modified TMMC (twice application of subconjunctival and subscleral MMC 0.2 mg/ml for 3 and 2 minutes, small internal block excision, laser suturelysis at 2 weeks) and subsequent posterior segment intervention with or without phacoemulsification. RESULTS: Preoperative IOP ranged from 30-80 mmHg, (mean 38.87 +/- 9.52). Follow-up period ranged from 12-47 months (mean 29 +/- 11.03). At final follow-up, qualified success (an IOP of < or = 21 mm Hg with or without medication) and complete success (an IOP of < or = 15 mm Hg without medication) was achieved in 21 (91.3%) of 23 eyes and in 12 (52.7%) of 23 eyes, respectively. The median successful period of maintaining qualified success was 13 months. Final visual acuity of 20/400 or better was preserved in 12 of 23 eyes (52.7%). None had hypotony maculopathy, leaking blebs or endophthalmitis. CONCLUSION: Early TMMC and subsequent posterior segment intervention, offerred a safe and prolonged satisfactory result of IOP control in NVG patients with hazy ocular media.

Posterior segment trauma: types of injuries, result of vitreo-retinal surgery and prophylactic broad encircling scleral buckle.

OBJECTIVES: To evaluate the result of pars plana vitrectomy (PPV) and prophylactic broad encirling scleral buckle in posterior segment trauma and to define factors that lead to functional failure. DESIGN: Retrospective, noncomparative, interventional case series. INTERVENTION: Prophylactic broad encircling scleral buckle, PPV, SF6/C3F8 or silicone oil implantation if required. RESULTS: Ninety-two patients (94 eyes) with open globe ocular injuries involving posterior segment, were treated between January 1988 and December 2004. The mean age was 33.1 years Common sources of injuries were industrial and automobile accidents. After a follow up period of at least 6 months, 62 of 94 eyes (65.96%) achieved visual acuity of 20/400 or better and 6 eyes (6.38%) lost vision to no light perception. Eyes that had sharp perforating injuries with retained IOFB had better visual outcome than the others. Twenty-three of 38 eyes (60.53%) that had sharp perforating injuries with retained IOFBs achieved a visual acuity of 20/70 or better Eyes with traumatic retinal detachment had a reattachment rate of 78.18% and a functional success rate of 56.36%. The detachment rate in vitrectomized eyes with prophylactic broad encircling scleral buckle was 3.19 %. Main reasons for functional failure (V.A. <20/400) were macular damage, retinal detachment with PVR and optic nerve injury. Endophthalmitis occurred in 6.25%. CONCLUSION: Sharp perforating ocular injuries have the best visual prognosis among all types of injuries. Pars plana vtrectomy and prophylactic broad encircling scleral buckle, can salvage and prevent subsequent retinal detachment in these severely traumatized eyes.

Choroidal osteoma in Oriental patients.

BACKGROUND: Choroidal osteoma is a rare tumour of the choroid. This is the first report of cases of choroidal osteoma in Thai patients. OBJECTIVE: To report the clinical characteristics, imaging findings and long-term follow-up of choroidal osteoma in four Oriental patients. METHOD: Four cases of choroidal osteoma were observed for 5 years or more. RESULTS: All patients were young female patients whose ages ranged from 24 to 37 years. Three were unilateral and one was bilateral. The tumors were located at the juxtapapillary and macular area with overlying serous retinal detachment. Two patients had previous thyroid diseases and one was pregnant when the tumors were diagnosed. Osteoma did not develop in the vicinity of posterior staphyloma of high myopic eyes. Echography showed acoustic features of a plano-convex sonically dense lesion with high reflectivity echoes which persisted despite lower system sensitivity. None had subretinal neovascularization. Subretinal fluid disappeared spontaneously within one to 14 months in three patients. Gradual growth of the tumor in a pseudopodium manner developed from two to six years after initial examination. Decalcification occurred spontaneously or after laser ablation. CONCLUSIONS: The authors presented four Oriental patients with choroidal osteoma who were observed for at least 5 years. Echography is the best method for identifying this lesion and has unique acoustic features. Subretinal fluid can be seen in the absence of subretinal neovascularization and resorbs spontaneously. Decalcification occurred as a natural process or after laser ablative treatment. Hormonal changes may implicate the development of this tumor.

Definite ocular sarcoidosis using endobronchial ultrasonography with transbronchial needle aspiration.

Purpose. To introduce a minimally invasive procedure, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), to obtain a pathologic evidence of a definite ocular sarcoidosis in a patient who initially presented with presumed ocular sarcoidosis with pulmonary involvement. Methods. An EBUS-TBNA procedure was performed at perihilar lymph nodes, subcarina, and right paratrachea of the patient and specimen obtained was sent for histocytopathological studies. Result. Histocytopathological findings revealed aggregates of epithelioid histiocytes forming a noncaseous granuloma, a hallmark of sarcoidosis. Conclusion. EBUS-TBNA should be considered an alternative procedure to provide cytohistopathology proven diagnosis of definite ocular sarcoidosis.