Long-term safety of the tafenoquine antimalarial chemoprophylaxis regimen: A 12-month, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Tafenoquine is a long-acting 8-aminoquinoline approved for antimalarial prophylaxis for ≤6 months. Additional data is needed to establish the drug's longer-term safety profile, including potential ophthalmic or neuropsychiatric effects. METHOD: This was a randomized, double-blind, placebo-controlled trial in 600 healthy adults. Eligible subjects were randomized 1:1 to receive tafenoquine 200 mg weekly (antimalarial prophylactic regimen) or placebo for 52 weeks. Scheduled safety visits occurred at Weeks 4, 12, 24, 52 (dosing completed), and 64 (final follow-up). Safety assessments included ophthalmic changes, general and neuropsychiatric adverse events (AEs), and laboratory value changes. RESULTS: The percentage of subjects with a protocol-defined Serious Ophthalmic Safety Event was lower in the Tafenoquine Group (18.2%) versus the Placebo Group (19%, p = 0.308). There was no significant difference between the percentages of subjects with at least one AE in the Tafenoquine Group (91.0%) versus Placebo (89.9%, p = 0.65). Common AEs seen at a significantly higher incidence for tafenoquine included reversible cornea verticillata (54.5%) and nausea (13.0%), leading to 0.0% and 0.7% discontinuations. Psychiatric AEs occurred at similar percentages in both study groups. Reversible changes in hemoglobin, methemoglobin, creatinine, and blood urea nitrogen (BUN) were noted. CONCLUSIONS: This study supports the safety of extended 52-week tafenoquine prophylaxis. CLINICAL TRIAL REGISTRATION NUMBER/CLINICALTRIALS. GOV IDENTIFIER: NCT03320174.

Pars plana vitrectomy versus combined pars plana vitrectomy-scleral buckle for primary repair of pseudophakic retinal detachment.

PURPOSE: To evaluate pars plana vitrectomy (PPV) versus a combined PPV and scleral buckle (PPV/SB) for repair of noncomplex, pseudophakic retinal detachment. DESIGN: Retrospective, nonrandomized, comparative interventional study. PARTICIPANTS: One hundred fifty-two eyes of 152 patients followed up for a mean of 10 months. The case series included 68 consecutive patients who underwent PPV and 84 consecutive patients who underwent a PPV/SB for primary repair of primary pseudophakic retinal detachment at Wills Eye Hospital between 2002 and 2004. METHODS: All primary PPV cases were performed by 2 surgeons who perform primary vitrectomy without regard to location of detachment, number and location of break(s), refractive error, or macula status. All primary PPV/SB were performed by a group of surgeons who solely perform PPV/SB on pseudophakic retinal detachments. All eyes underwent a standard 3-port 20-gauge PPV under wide-field viewing and scleral depression. Endolaser photocoagulation was applied either around the retinal tears or 360 degrees to the vitreous base region followed by gas tamponade. Patients with proliferative vitreoretinopathy grade C or worse were excluded from the study. MAIN OUTCOME MEASURES: (1) Single surgery anatomic success rates, (2) preoperative and postoperative visual acuity, and (3) complications. RESULTS: The single surgery anatomic success rate in the primary PPV group was 63 of 68 eyes (92.6%; 95% confidence interval [CI], 84%-98%) and in the primary PPV/SB group was 79 of 84 eyes (94.0%; 95% CI, 87%-98%). Both groups obtained 100% final reattachment rate. There was no statistically significant difference between the success rates (P = 0.75, Fisher exact test). The PPV group's best-corrected postoperative visual acuity demonstrated a +0.10 logarithm of the minimum angle of resolution improvement over the PPV/SB group (P = 0.07). The PPV group had a smaller incidence of postoperative complications (13/68 patients [19.1%] vs. 27/84 patients [32.1%]; P = 0.10, Fisher exact test). CONCLUSIONS: Primary PPV and PPV/SB seem to have similar efficacy in the repair of a matched group of patients with primary noncomplex pseudophakic retinal detachment. There was no statistically significant difference in complication rate between the 2 groups.

Intravitreal triamcinolone acetonide for diabetic macular edema.

PURPOSE: Intravitreal injection of triamcinolone acetonide has been advocated to treat exudative diabetic macular edema. The purpose of the study was to evaluate the clinical outcome of an intravitreal injection of triamcinolone acetonide as treatment for diffuse diabetic macular edema. METHODS: This study was a retrospective, interventional, clinical case series examining 210 eyes of 174 patients who received an intravitreal injection of 1 or 4 mg of triamcinolone acetonide for treatment of diffuse diabetic macular edema. Inclusion criteria were clinically significant macular edema, visual acuity loss, and leakage shown by fluorescein angiography. Main outcome measures were visual acuity and intraocular pressure. Mean follow-up time +/- SD was 6.6 +/- 3.1 months. RESULTS: In the study group, visual acuity improved significantly (P < 0.001) from a median of 20/200 (mean logMAR, 0.92) at baseline to 20/80 (mean logMAR, 0.82) at 6 months. Mean intraocular pressure +/- SD increased from 15.4 +/- 3.4 mmHg (median, 16 mmHg; range, 6-26 mmHg) to a maximal value of 20.4 +/- 6.2 mmHg (median, 19 mmHg; range, 12-51 mmHg) during the follow-up period. Complications included culture-negative sterile endophthalmitis in six cases and cataract extraction in five eyes. CONCLUSIONS: Intravitreal injection of 1 to 4 mg of triamcinolone acetonide may benefit patients by improving visual acuity in eyes with clinically significant diabetic macular edema. This study did not provide significant evidence to justify its routine use in clinical practice for all patients with diabetic macular edema. A randomized clinical trial on this issue would provide more conclusive evidence and help identify those patients most likely to benefit from intravitreal triamcinolone acetonide.

Optical coherence tomography of chronic solar retinopathy.

PURPOSE: To describe the optical coherence tomographic findings in eight eyes of four patients with chronic solar retinopathy. All patients had a history of sun gazing months to years prior to presentation. DESIGN: Retrospective case series. METHODS: Patients were examined using biomicroscopy performed by two or more experienced vitreoretinal specialists. All eight eyes had optical coherence tomography performed at the time of initial examination. RESULTS: All patients had a history of sun gazing and decreased vision in both eyes. On biomicroscopy, all eyes had a small, irregularly-shaped lamellar defect in the foveal center. No posterior vitreous detachment was present in any eye. Optical coherence tomography revealed a hyporeflective space at the level of the outer neurosensory retina and retinal pigment epithelium in all eyes. CONCLUSION: Optical coherence tomography demonstrates a characteristic hyporeflective space in the outer retina in patients with chronic solar retinopathy. These findings correlate with the histopathology of this condition and may be a useful clinical tool in confirming its diagnosis.

Infectious and presumed noninfectious endophthalmitis after intravitreal triamcinolone acetonide injection.

PURPOSE: To report potentially distinguishing characteristics between bacterial endophthalmitis and presumed noninfectious endophthalmitis associated with intravitreal triamcinolone acetonide injection. METHODS: Records of two patients with culture-proven bacterial endophthalmitis and six patients with presumed noninfectious endophthalmitis from intravitreal triamcinolone acetonide injections were analyzed retrospectively. RESULTS: Two eyes in two patients with culture-proven bacterial endophthalmitis had decreased vision and hypopyon or vitritis, but no pain or conjunctival injection 2 weeks after intravitreal triamcinolone acetonide injection. Seven eyes in six patients with presumed noninfectious endophthalmitis had blurred vision, hypopyon, and variable pain all within 2 days of intravitreal triamcinolone injection. All seven eyes were followed up closely and had rapid resolution of hypopyon and symptoms. CONCLUSION: Bacterial endophthalmitis after intravitreal triamcinolone acetonide injection may present in an atypical, relatively delayed manner with decreased vision but no pain or redness. Presumed noninfectious endophthalmitis presents within 2 days after the injection, may be accompanied by discomfort, and has a hypopyon that may be the triamcinolone material itself or a sterile inflammatory reaction. In these eyes, the hypopyon and symptoms quickly resolve without treatment.

Surgical ablation of retinal angiomatous proliferation.

Age-related macular degeneration (AMD) remains the leading cause of visual loss in adults older than 65 years. Retinal angiomatous proliferation (RAP) is a newly recognized manifestation of exudative AMD that has a poor natural history and demonstrated resistance to treatment with conventional laser photocoagulation. A novel surgical technique has been developed in this pilot series that shows promise in the treatment of this subtype of neovascular lesions. Through specific surgical lysis of the feeding arteriole and draining venule of an RAP lesion, improvement in visual acuity has been noted. This has been correlated with resolution of intraretinal edema and flattening of associated pigment epithelial detachment, which was confirmed by fluorescein angiography, optical coherence tomography, and high-speed indocyanine green angiography.

Photodynamic therapy of polypoidal choroidal vasculopathy.

Polypoidal choroidal vasculopathy is an abnormality of the choroidal vasculature characterized by aneurysmal-like budding of the vessels with exudation and recurrent serosanguinous detachments of the retinal pigment epithelium. Treatment is limited to laser photocoagulation of leaking vessels, which is used when vision is decreased, or exudate and hemorrhage threaten or involve the fovea. This article describes a patient with polypoidal choroidal vasculopathy successfully treated with photodynamic therapy using verteporfin.

Managing cystoid macular edema after cataract surgery.

Cystoid macular edema (CME) is a common problem after cataract extraction. It can occur after uncomplicated surgery in patients with otherwise healthy eyes, after complicated surgery, or after surgery in patients with ocular diseases such as uveitis or diabetic retinopathy. Usually vision loss from cystoid macular edema is temporary and responds to treatment with topical anti-inflammatory medications. However, some cases respond poorly to conservative treatment and may develop permanent visual loss. A review of the medical literature was performed for all articles published in English between August 1, 2001 and July 31, 2002 on the topic of cystoid macular edema after cataract surgery. The authors selected nine articles that were most relevant to the practicing ophthalmologist for inclusion in this review. Topics of interest included vitreous loss, retained lens fragments, diabetes, uveitis, retinitis pigmentosa, ocular hypotensive lipids, internal limiting membrane peeling, and intravitreal triamcinolone injection.

Optical coherence tomography findings following photodynamic therapy of choroidal neovascularization.

PURPOSE: To develop an optical coherence tomography (OCT) classification system that monitors the response of eyes treated with photodynamic therapy (PDT) with verteporfin for subfoveal choroidal neovascularization (CNV) from age-related macular degeneration (AMD). DESIGN: Retrospective interventional case series. METHODS: Ninety eyes (88 patients) with AMD and predominantly classic subfoveal CNV treated with PDT using verteporfin were identified by a laser log and retrospectively reviewed. Optical coherence tomography and fluorescein angiography (FA) were performed before treatment and at subsequent follow-up examinations in all eyes. Optical coherence tomography findings were evaluated and compared with corresponding FA. RESULTS: A five-stage OCT classification of eyes treated with PDT was created from the evaluation of 79 total eyes (77 patients). Stage I (two eyes) is recognized within the first week of treatment and demonstrates an acute inflammatory response with increased subretinal fluid. Stage II (28 eyes) represents the restoration of a near-normal fovea contour with diminished subretinal fluid occurring 1 to 4 weeks after treatment. Stage III (79 eyes) occurs between 4 to 12 weeks following treatment and is subdivided into two categories based on the amount of subretinal fibrosis and fluid present. Stage IIIa (15 eyes) contains a greater subretinal fluid to fibrosis ratio indicating an active CNV process. Lesions in stage IIIb (64 eyes) less actively leak and have more prominent fibrosis with minimal intraretinal fluid. Cystoid macular edema defines a stage IV lesion (11 eyes). In stage V lesions (19 eyes) the subretinal fluid resolves with thinning of the retina as well as fibrosis merging with the retinal pigment epithelial layer (RPE). CONCLUSION: Optical coherence tomography appears to be useful in monitoring the retinal changes that occur following PDT of CNV and may assist in understanding the changes observed on angiography.

Transient multifocal electroretinogram dysfunction in multiple evanescent white dot syndrome.

A 22-year-old female patient with acute monocular scotomata after an upper respiratory infection and the fluorescein angiographic findings consistent with the diagnosis of multiple evanescent white dot syndrome (MEWDS) is described. Unlike full-field ERG, which shows a generalized depressed signal in MEWDS, the authors showed areas of depressions corresponding to the scotomata using multifocal electroretinogram (MFERG). The MFERG abnormalities seen at presentation resolved with the resolution of clinical symptoms after 6 weeks, in contrast to a previous report. The MFERG may be a useful tool to further characterize MEWDS and other blind-spot enlarging syndromes.

Intravitreal triamcinolone for refractory diabetic macular edema.

PURPOSE: To determine if intravitreal injection of triamcinolone acetonide is safe and effective in treating diabetic macular edema unresponsive to prior laser photocoagulation. DESIGN: Prospective, noncomparative, interventional case series. PARTICIPANTS: Sixteen eyes with clinically significant diabetic macular edema (CSME) that failed to respond to at least two previous sessions of laser photocoagulation. METHODS: Eyes were diagnosed with CSME and treated with at least two sessions of laser photocoagulation according to Early Treatment Diabetic Retinopathy Study guidelines. At least 6 months after initial laser therapy, the response was measured by clinical examination and optical coherence tomography (OCT). Eyes with a residual central macular thickness of more than 300 microm (normal, 200 microm) and visual loss from baseline were offered intravitreal injection of 4 mg triamcinolone acetonide. The visual and anatomic responses were observed as well as complications related to the injection procedure and corticosteroid medication. MAIN OUTCOME MEASURES: Visual acuity and quantitative change in OCT macular thickening were assessed. Potential complications were monitored, including intraocular pressure response, cataract progression, retinal detachment, vitreous hemorrhage, and endophthalmitis. RESULTS: All patients completed 3 months of follow-up, and 8 of 16 patients (50%) completed 6 or more months of follow-up. Mean improvement in visual acuity measured 2.4, 2.4, and 1.3 Snellen lines at the 1-, 3-, and 6-month follow-up intervals, respectively. The central macular thickness as measured by OCT decreased by 55%, 57.5%, and 38%, respectively, over these same intervals from an initial pretreatment mean of 540.3 microm (+/-96.3 microm). Intraocular pressure exceeded 21 mmHg in 5, 3, and 1 eye(s), respectively, during these intervals. One eye exhibited cataract progression at 6 months. No other complications were noted over a mean follow-up of 6.2 months. Reinjection was performed in 3 of 8 eyes after 6 months because of recurrence of macular edema. CONCLUSIONS: Intravitreal triamcinolone is a promising therapeutic method for diabetic macular edema that fails to respond to conventional laser photocoagulation. Complications do not appear to be prohibitive. Further study is warranted to assess the long-term efficacy and safety, and the need for retreatment.

Treating cytomegalovirus retinitis-related retinal detachment by combining silicone oil tamponade and ganciclovir implant.

BACKGROUND AND OBJECTIVE: With the efficacy of pars plana vitrectomy and silicone oil infusion in treating cytomegalovirus (CMV) retinitis-related retinal detachment and the success of the ganciclovir implant in controlling CMV retinitis, we sought to evaluate the possible benefits of combining these two procedures in one surgical operation. PATIENTS AND METHODS: A retrospective review of 10 patients was conducted. Each patient was diagnosed with a CMV retinitis-related retinal detachment and treated with pars plana vitrectomy and silicone oil infusion, with simultaneous placement of a ganciclovir implant. Parameters evaluated included location of retinal detachment, reattachment rate, pre- and post-operative Snellen visual acuity, pre- and post-operative CMV retinitis activity and location, and complications of the combined procedure. RESULTS: Overall anatomic reattachment was achieved in all 10 patients. Four patients presented with macular involvement of their retinal detachments. Three of these patients experienced significant post-operative improvement in visual acuity. Surgery preserved visual acuity in the 6 patients who presented with macula attached. Best postoperative acuity was better than or equal to 20/100 in 7 (70%) patients. All 3 CMV retinitis patients with inactive retinitis preoperatively remained free of retinitis for the duration of follow up. At last follow up, 8/10 (80%) showed no active CMV retinitis and no patients experienced progression of their retinitis. CONCLUSIONS: Results of this series indicate that patients benefit from excellent anatomic reattachment rates, preservation or improvement of visual acuity in most cases, and extended control of their CMV retinitis. Combining the two procedures appears viable. Further study is warranted to assess definitive anatomic and functional outcomes resulting from this new technique.

Multifocal electroretinography response after laser photocoagulation of a subretinal nematode.

PURPOSE: To describe multifocal electroretinography findings before and after laser photocoagulation of a subretinal nematode in diffuse unilateral subacute neuroretinitis. METHOD: Observational case report. A 45-year-old woman with left eye inflammation, subretinal tracts superior and temporal to the fovea, and a subretinal coiled mobile parasite was treated with laser photocoagulation to destroy the nematode. Multifocal electroretinography was performed before and after laser photocoagulation. RESULTS: In the left eye, multifocal electroretinography before treatment showed decreased foveal response density and increased parafoveal and perifoveal waveform amplitudes. Two months after laser photocoagulation, multifocal electroretinography showed full recovery of normal findings and the visual acuity remained 20/20. CONCLUSION: Multifocal electroretinography appears to be useful in evaluating the retinal findings after photocoagulation of a parasite associated with diffuse unilateral subacute neuroretinitis.