Meidong Zhu

Five-year Results of a Randomized Trial with Open-label Extension of Triamcinolone Acetonide for Refractory Diabetic Macular Edema

OBJECTIVE To report 5-year outcomes from a clinical trial of intravitreal triamcinolone acetonide (IVTA) in eyes with diabetic macular edema (DME) and impaired vision despite previous laser treatment. DESIGN Prospective, double-masked, randomized clinical trial. After completing the 2-year visit, all eyes, including those initially randomized to receive placebo, received IVTA according to prospectively defined guidelines. PARTICIPANTS AND CONTROLS A total of 69 eyes (41 patients) were entered into the study, with 34 eyes initially receiving active treatment and 35 eyes receiving placebo. Five-year data were available for 44 of 67 eyes (66%). For the 23 eyes with missing 5-year data, of which 13 received placebo and 10 received IVTA, the last observation was carried forward. INTERVENTION Intravitreal injection of 0.1 ml of 40 mg/ml triamcinolone acetonide with adjunctive laser therapy where appropriate. MAIN OUTCOME MEASURES Improvement of best-corrected logarithm of the minimum angle of resolution visual acuity by >or=5 letters after 5 years compared with baseline and 2 years, and incidence of adverse events. Secondary outcome was the change in central macular thickness. RESULTS Improvement of >or=5 letters after 5 years was found in 14 of 33 eyes (42%) initially treated with IVTA compared with 11 of 34 eyes (32%) initially treated with placebo (z(GEE) = 0.81, P = 0.4). Foveal thickness decreased by 30 microm (95% confidence interval, -47 to 107 microm) less in the initial-IVTA group than in the initial-placebo group at 5 years (z(GEE) = 0.76, P = 0.45); 5 of 11 eyes (45%) from the initial-IVTA group that were phakic at commencement of the third year required cataract surgery. A similar number of eyes from each group required ongoing treatment from the third year onward with both laser and IVTA, indicating that IVTA treatment for 2 years does not lead to reduction in the risk of recurrent edema. CONCLUSIONS The majority of eyes that initially improved with IVTA maintained their gain after 5 years. No new safety concerns were identified. IVTA treatment may be considered in carefully selected cases of impaired vision caused by advanced DME that are unresponsive to other interventions.

Loss of Müller's cells and photoreceptors in macular telangiectasia type 2.

PURPOSE To correlate postmortem histology from a patient with macular telangiectasia (MacTel) type 2 with previously recorded clinical imaging data. DESIGN Observational clinicopathologic case report. METHODS The distribution of retinal blood vessels was used to map the location of serial wax sections in color fundus and optical coherence tomography (OCT) images. Fluorescent immunohistochemistry was used to visualize markers for Müllers cells (vimentin and retinaldehyde-binding protein 1), photoreceptors (L-M opsin, rhodopsin, and cytochrome oxidase 2), and the outer limiting membrane (OLM) (zonula occludens 1 and occludin). MAIN OUTCOME MEASURES Distribution of specific markers in immunohistochemistry on retinal sections through the fovea in relation to clinical data. RESULTS The clinically recorded region of macular pigment loss in the macula correlated well with Müllers cell depletion. The OCT data showed a loss of the photoreceptor inner segment/outer segment (IS/OS) junction in the central retina, which correlated well with rod loss but not with cone loss. Markers for the OLM were lost where Müllers cells were lost. CONCLUSIONS We have confirmed our previous finding of Müllers cell loss in MacTel type 2 and have shown that the area of Müllers cell loss matches the area of macular pigment depletion. In this patient, the IS/OS junction seen by OCT was absent in a region where rods were depleted but cones were still present.

Familial Asymptomatic Macular Telangiectasia Type 2

OBJECTIVE To report findings in asymptomatic family members of patients with macular telangiectasia type 2. DESIGN Prospective, observational, cross-sectional case series. PARTICIPANTS Four patients with symptomatic macular telangiectasia type 2 (index patients) and 5 relatives, including 2 sets of monozygotic twins. METHODS Screening of family members of participants in a non-interventional natural history study of macular telangiectasia type 2. Ophthalmologic examination included best-corrected visual acuity testing, fundus biomicroscopy, fluorescein angiography (FA), optical coherence tomography (OCT), and fundus autofluorescence (FAF) imaging. MAIN OUTCOME MEASURES Evidence for macular telangiectasia type 2 in any of the imaging methods used and visual function of the family members studied. RESULTS In the first family, 2 of 3 daughters of a severely affected 68-year-old woman had features of macular telangiectasia type 2. Although one of the daughters was diagnosed by biomicroscopic examination, the second daughter was diagnosed only by subtle changes on OCT and FAF imaging. Both affected daughters were asymptomatic and were unaware that they had the condition. In the second family, clinical examination showed that the 60-year-old brother of the 75-year-old index patient obviously was affected, despite a lack of any subjective visual dysfunction. The 65-year-old monozygotic twin of the third index patient showed a slight retinal thinning within a small area temporal to the foveola in both eyes as well as minor staining on FA and a subtle monocular loss of macular pigment. The 56-year-old asymptomatic monozygotic twin of the last proband had opacification of the retina with leakage on FA in the right eye. The fellow eye was unremarkable except for an abnormal FAF signal that was present in both eyes. CONCLUSIONS Macular telangiectasia type 2 may be more common than previously assumed, but patients may not seek ophthalmic care if their visual function is normal. The study of these early, asymptomatic cases may yield valuable insights into the pathogenesis of the condition. Further research is warranted to determine whether there is an underlying, dominantly inherited genetic abnormality in macular telangiectasia type 2 of variable penetrance and expressivity.

Intravitreal Triamcinolone Prior to Laser Treatment of Diabetic Macular Edema: 24-Month Results of a Randomized Controlled Trial

PURPOSE To report the 24 months outcomes from a clinical trial of intravitreal triamcinolone acetonide (IVTA) plus laser versus laser treatment only in eyes with diabetic macular edema (DME). DESIGN Prospective, double-masked, randomized, placebo-controlled study. PARTICIPANTS Eighty-four eyes of 54 participants were entered into the study, with 42 eyes randomly assigned to receive IVTA plus laser and 42 randomly assigned to receive laser treatment alone. Primary end point data were available for 71 (84.5%) eyes at 24 months, with last visual acuity observation carried forward for the remaining eyes. METHODS Best-corrected logarithm of minimum angle of resolution (logMAR) visual acuity and central macular thickness (CMT) by optical coherence tomography were measured after laser treatment preceded by either IVTA or sham. MAIN OUTCOMES MEASURES The primary outcome was the proportion of eyes with improvement in visual acuity of 10 letters or more at 24 months. The secondary outcomes were mean visual acuity, requirement for further treatment, change in CMT, and adverse events. RESULTS At 24 months, improvement of 10 logMAR letters or more was seen in 15 (36%) of 42 eyes treated with IVTA plus laser compared with 7 (17%) of 42 eyes treated with laser only (P = 0.047; odds ratio, 2.79; 95% confidence interval, 1.01-7.67). There was no difference in the mean CMT or mean logMAR visual acuity between 2 groups. At least 1 retreatment was required in the second year of the study in 29 (69%) of 42 IVTA plus laser-treated eyes compared with 19 (45%) of 42 laser only eyes (P = 0.187). Cataracts were removed from 17 (61%) of 28 phakic IVTA plus laser-treated eyes versus 0 (0%) of 27 laser only eyes (P<0.001). Treatment for elevated intraocular pressure was required in 27 (64%) of 42 IVTA plus laser eyes compared with 10 (24%) of 42 laser only eyes (P<0.001). CONCLUSIONS Treatment with IVTA plus laser resulted in a doubling of improvement in vision by 10 letters or more compared with laser only over 2 years in eyes with DME, but is associated with cataract and raised intraocular pressure.

Efficacy and Safety of Multiple Intravitreal Triamcinolone Injections for Refractory Diabetic Macular Oedema.

Aim: The efficacy and safety of repeated injections of intravitreal triamcinolone (IVTA) for diabetic macular oedema is unclear, with results of previous reports conflicting. Methods: This is a prospective, observational case series of 27 eyes receiving IVTA for diabetic macular oedema. LogMAR visual acuity (VA) and central macular thickness (CMT) were measured at baseline and in 3 to 6 monthly intervals for up to 24 months, then correlated with the number of IVTA injections given. Results: One IVTA injection was required in 6 (18%) eyes, 2 in 8 (24%) eyes, 3 in 13 (39%) eyes and 4–5 in 6 (18%) eyes. VA improved in all patients, but neither the final improvement in VA nor the absolute improvement in CMT from baseline to 24 months correlated with the number of injections received (p = 0.44 and 0.84, respectively). Cataract surgery was more frequent in eyes receiving more injections (p = 0.01). Conclusions: This study suggests that repeated injections of IVTA continue to be as effective as the first over a 2-year period. The probability of cataract surgery increases with an increasing number of injections.

Original articleIntravitreal Triamcinolone Prior to Laser Treatment of Diabetic Macular Edema: 24-Month Results of a Randomized Controlled Trial

PURPOSE To report the 24 months outcomes from a clinical trial of intravitreal triamcinolone acetonide (IVTA) plus laser versus laser treatment only in eyes with diabetic macular edema (DME). DESIGN Prospective, double-masked, randomized, placebo-controlled study. PARTICIPANTS Eighty-four eyes of 54 participants were entered into the study, with 42 eyes randomly assigned to receive IVTA plus laser and 42 randomly assigned to receive laser treatment alone. Primary end point data were available for 71 (84.5%) eyes at 24 months, with last visual acuity observation carried forward for the remaining eyes. METHODS Best-corrected logarithm of minimum angle of resolution (logMAR) visual acuity and central macular thickness (CMT) by optical coherence tomography were measured after laser treatment preceded by either IVTA or sham. MAIN OUTCOMES MEASURES The primary outcome was the proportion of eyes with improvement in visual acuity of 10 letters or more at 24 months. The secondary outcomes were mean visual acuity, requirement for further treatment, change in CMT, and adverse events. RESULTS At 24 months, improvement of 10 logMAR letters or more was seen in 15 (36%) of 42 eyes treated with IVTA plus laser compared with 7 (17%) of 42 eyes treated with laser only (P = 0.047; odds ratio, 2.79; 95% confidence interval, 1.01-7.67). There was no difference in the mean CMT or mean logMAR visual acuity between 2 groups. At least 1 retreatment was required in the second year of the study in 29 (69%) of 42 IVTA plus laser-treated eyes compared with 19 (45%) of 42 laser only eyes (P = 0.187). Cataracts were removed from 17 (61%) of 28 phakic IVTA plus laser-treated eyes versus 0 (0%) of 27 laser only eyes (P<0.001). Treatment for elevated intraocular pressure was required in 27 (64%) of 42 IVTA plus laser eyes compared with 10 (24%) of 42 laser only eyes (P<0.001). CONCLUSIONS Treatment with IVTA plus laser resulted in a doubling of improvement in vision by 10 letters or more compared with laser only over 2 years in eyes with DME, but is associated with cataract and raised intraocular pressure.

Response Of Pigment Epithelial Detachments To Intravitreal Aflibercept Among Patients With Treatment-resistant Neovascular Age-related Macular Degeneration

Purpose: To assess the effect of intravitreal aflibercept on pigment epithelial detachment (PED) in patients with treatment-resistant neovascular age-related macular degeneration. Methods: Forty-six patients with vascularized PEDs participating in a wider, prospective clinical trial of treatment-resistant neovascular age-related macular degeneration received 2-mg aflibercept as 3 loading doses 1 month apart, followed by further 2-monthly doses over a total 12-month period. Change in PED dimensions and reflective properties were assessed by optical coherence tomography. Reflectivity was subclassified as solid (hyperreflective), hollow (hyporeflective), or mixed (elements of both). Results: Aflibercept reduced PED height, width, and length at 48 weeks compared with baseline values (P ⩽ 0.01 for all). Reductions in PED height were correlated with reductions in central macular thickness at 48 weeks (R2 = 0.36, P < 0.001). There was no significant correlation between PED height decrease and visual acuity changes at 48 weeks. Solid PEDs were less likely to experience reductions in all three dimensions than either hollow or mixed PEDs. Conclusion: Aflibercept is effective in reducing PED dimensions in treatment-resistant patients and is most effective in PEDs demonstrating some hyporeflective optical coherence tomography characteristics. Reduction in PED dimensions correlated with central macular thickness, but not with visual acuity changes. The role of PEDs as markers of disease requires further investigation; however, lesions should be monitored for retinal fluid recurrence.

Triamcinolone-induced cataract in eyes with diabetic macular oedema: 3-year prospective data from a randomized clinical trial

Purpose:  To describe the 3‐year risk of cataract after intravitreal triamcinolone (IVTA) injections for diabetic macular oedema and the outcomes of cataract surgery.

Retinal Vascular Caliber Changes after Intravitreal Triamcinolone Treatment for Diabetic Macular Edema

PURPOSE To describe the changes in retinal vascular caliber in response to a single injection of intravitreal triamcinolone (IVTA) in patients with refractory diabetic macular edema. METHODS Prospective data from a randomized clinical trial were used. The effects of IVTA versus sham injections in patients with refractory diabetic macular edema were evaluated in a randomized clinical trial involving 69 eyes of 43 patients. Of these, 28 eyes (15 IVTA and 13 sham) of 21 patients had gradable retinal photographs at the baseline and 3-month follow-up visit for analysis in the present study. Retinal vascular caliber was measured from digital fundus photographs and summarized as central retinal artery (CRAE) and vein (CRVE) equivalents in all eyes at baseline and at the 3-month follow-up visit. RESULTS Over the 3 months of the study, there was a significant reduction compared to baseline in retinal arteriolar (147.8 microm vs. 140.0 microm, P = 0.047) and venular (219.5 microm vs. 198 microm, P = 0.039) caliber in eyes treated with IVTA. There was no change in retinal arteriolar (139.9 microm vs. 139.2 microm, P = 0.878) or venular (220.3 microm vs. 217.6 microm, P = 0.534) caliber in those treated with sham injections. CONCLUSIONS IVTA has a significant narrowing effect on both retinal arteriolar and venular diameter in eyes with diabetic macular edema (ClinicalTrials.gov number, NCT00148330).

Rapid reduction of hard exudates in eyes with diabetic retinopathy after intravitreal triamcinolone: data from a randomized, placebo-controlled, clinical trial

Purpose:  To assess the effect of triamcinolone acetonide over 3 months on hard exudates in patients with diabetic macular oedema (DMO).