Ruth Axer-Siegel

Efficacy and Safety of Monthly versus Quarterly Ranibizumab Treatment in Neovascular Age-related Macular Degeneration: The EXCITE Study

OBJECTIVE To demonstrate noninferiority of a quarterly treatment regimen to a monthly regimen of ranibizumab in patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). DESIGN A 12-month, multicenter, randomized, double-masked, active-controlled, phase IIIb study. PARTICIPANTS Patients with primary or recurrent subfoveal CNV secondary to AMD (353 patients), with predominantly classic, minimally classic, or occult (no classic component) lesions. INTERVENTION Patients were randomized (1:1:1) to 0.3 mg quarterly, 0.5 mg quarterly, or 0.3 mg monthly doses of ranibizumab. Treatment comprised of a loading phase (3 consecutive monthly injections) followed by a 9-month maintenance phase (either monthly or quarterly injection). MAIN OUTCOME MEASURES Mean change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to month 12 and the incidence of adverse events (AEs). RESULTS In the per-protocol population (293 patients), BCVA, measured by Early Treatment Diabetic Retinopathy Study-like charts, increased from baseline to month 12 by 4.9, 3.8, and 8.3 letters in the 0.3 mg quarterly (104 patients), 0.5 mg quarterly (88 patients), and 0.3 mg monthly (101 patients) dosing groups, respectively. Similar results were observed in the intent-to-treat (ITT) population (353 patients). The mean decrease in CRT from baseline to month 12 in the ITT population was -96.0 μm in 0.3 mg quarterly, -105.6 μm in 0.5 mg quarterly, and -105.3 μm in 0.3 mg monthly group. The most frequent ocular AEs were conjunctival hemorrhage (17.6%, pooled quarterly groups; 10.4%, monthly group) and eye pain (15.1%, pooled quarterly groups; 20.9%, monthly group). There were 9 ocular serious AEs and 3 deaths; 1 death was suspected to be study related (cerebral hemorrhage; 0.5 mg quarterly group). The incidences of key arteriothromboembolic events were low. CONCLUSIONS After 3 initial monthly ranibizumab injections, both monthly (0.3 mg) and quarterly (0.3 mg/0.5 mg) ranibizumab treatments maintained BCVA in patients with CNV secondary to AMD. At month 12, BCVA gain in the monthly regimen was higher than that of the quarterly regimens. The noninferiority of a quarterly regimen was not achieved with reference to 5.0 letters. The safety profile was similar to that reported in prior ranibizumab studies.

Diabetic Retinopathy during Pregnancy

PURPOSE The purpose of the study is to evaluate the incidence, prevalence, progression, and risk factors of diabetic retinopathy during pregnancy. METHODS Sixty-five patients who were pregnant and had insulin-dependent diabetes mellitus were evaluated before pregnancy, in every trimester during the pregnancy, and 12 months postpartum. The medical data included age, diabetes duration, glycohemoglobin, fructosamine, hemoglobin, creatinine, uric acid, and systolic and diastolic blood pressure. RESULTS Progression of the retinopathy occurred in 77.5% of the patients who presented with diabetic retinopathy at conception; proliferative diabetic retinopathy occurred in 22.5%. Only 26% of the patients who started the pregnancy without diabetic retinopathy had some progression of the retinopathy. Duration of the diabetes was longer in the progressive group compared with the nonprogressive group (P = 0.007). The glycohemoglobin was higher in the progressive group than in the nonprogressive group at each time point, but only in the third trimester was the difference statistically significant (P = 0.04). The hemoglobin level was lower in the progressive group than in the nonprogressive group (P < 0.01). The systolic blood pressure was higher in the progressive group (P < 0.005). CONCLUSION Understanding the risk factors contributing to the aggravation of diabetic retinopathy during pregnancy is helpful in designing criteria for the team management of pregnant patients with diabetes.

Association of neovascular age-related macular degeneration and hyperhomocysteinemia

PURPOSE To assess the relationship between plasma homocysteine levels and exudative neovascular age-related macular degeneration (AMD). DESIGN Cross-sectional study. METHODS A prospective comparative cross-sectional study was conducted in outpatient ophthalmology clinics in a university-affiliated medical institution. The cohort consisted of 59 patients (25 male, 34 female) with a mean age of 78 years (standard deviation [SD] = 8.4) with neovascular AMD who were candidates for photodynamic treatment. Patients were compared for plasma homocysteine levels with 58 patients who had dry AMD (24 male, 34 female) with a mean age of 76.3 years (SD = 8.4) and with a control group of 56 age-matched subjects (27 male, 29 female), with a mean age of 77.3 years (SD = 8.2). A 3-ml venous blood sample was obtained from each participant after an 8-hour fast. Levels of plasma homocysteine were measured by high performance liquid chromatography. The main outcome measure was hyperhomocysteinemia, defined as a plasma homocysteine level above 15 micromol/l. RESULTS Homocysteine levels were higher by 27.9% in the neovascular AMD than in the dry AMD group, and by 21.9% than in the control group (P <.02). Hyperhomocysteinemia was found in 44.1% of the study group, in 22.4% of the dry AMD group, and in 21.4% of the control group (P =.011). CONCLUSIONS This study suggests an association between an elevated plasma level of homocysteine and exudative neovascular AMD but not dry AMD.

Cystoid macular edema after cataract surgery with intraocular vancomycin

OBJECTIVE To determine whether the use of supplemental prophylactic vancomycin in the irrigating solution during extracapsular lens extraction is associated with increased incidence of cystoid macular edema. DESIGN Prospective, randomized, double-masked clinical study. PARTICIPANTS Consecutive series of 118 patients 60 years of age or older undergoing cataract surgery. INTERVENTION The study group received an irrigating balanced salt solution supplemented with vancomycin (10 microg/ml), and the control group received the salt solution only. Fluorescein angiography was performed 1 and 4 months after surgery. MAIN OUTCOME MEASURES Evidence of angiographic and clinical cystoid macular edema, and visual acuity at 1 and 4 months after surgery. RESULTS The rate of postoperative angiographic cystoid macular edema was significantly higher in the study patients than in the control group at 1 month (55% vs. 19%, P = 0.0006) and 4 months (26% vs. 4%, P = 0.0099). The rates of clinical macular edema were 23% and 7%, respectively, at 1 month (P = 0.011) and 20% versus 0% at 4 months (P = 0.006). Visual acuity of 20/30 or better was noted at 4 months after surgery in 76% of the study group compared to 95.5% of the control group. CONCLUSIONS The role of preventive intracameral vancomycin during intraocular surgery should be reassessed in view of the associated increase in the incidence of angiographic cystoid macular edema.

The SECURE study:long-term safety of Ranibizumab 0.5 mg in neovascular age-related macular degeneration

OBJECTIVE To evaluate long-term safety of intravitreal ranibizumab 0.5-mg injections in neovascular age-related macular degeneration (nAMD). DESIGN Twenty-four-month, open-label, multicenter, phase IV extension study. PARTICIPANTS Two hundred thirty-four patients previously treated with ranibizumab for 12 months in the EXCITE/SUSTAIN study. METHODS Ranibizumab 0.5 mg administered at the investigators discretion as per the European summary of product characteristics 2007 (SmPC, i.e., ranibizumab was administered if a patient experienced a best-corrected visual acuity [BCVA] loss of >5 Early Treatment Diabetic Retinopathy Study letters measured against the highest visual acuity [VA] value obtained in SECURE or previous studies [EXCITE and SUSTAIN], attributable to the presence or progression of active nAMD in the investigators opinion). MAIN OUTCOME MEASURES Incidence of ocular or nonocular adverse events (AEs) and serious AEs, mean change in BCVA from baseline over time, and the number of injections. RESULTS Of 234 enrolled patients, 210 (89.7%) completed the study. Patients received 6.1 (mean) ranibizumab injections over 24 months. Approximately 42% of patients had 7 or more visits at which ranibizumab was not administered, although they had experienced a VA loss of more than 5 letters, indicating either an undertreatment or that factors other than VA loss were considered for retreatment decision by the investigator. The most frequent ocular AEs (study eye) were retinal hemorrhage (12.8%; 1 event related to study drug), cataract (11.5%; 1 event related to treatment procedure), and increased intraocular pressure (6.4%; 1 event related to study drug). Cataract reported as serious due to hospitalization for cataract surgery occurred in 2.6% of patients; none was suspected to be related to study drug or procedure. Main nonocular AEs were hypertension and nasopharyngitis (9.0% each). Arterial thromboembolic events were reported in 5.6% of the patients. Five (2.1%) deaths occurred during the study, none related to the study drug or procedure. At month 24, mean BCVA declined by 4.3 letters from the SECURE baseline. CONCLUSIONS The SECURE study showed that ranibizumab administered as per a VA-guided flexible dosing regimen recommended in the European ranibizumab SmPC at the investigators discretion was well tolerated over 2 years. No new safety signals were identified in patients who received ranibizumab for a total of 3 years. On average, patients lost BCVA from the SECURE study baseline, which may be the result of disease progression or possible undertreatment. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Diode laser treatment of posterior retinopathy of prematurity

AIMS To study the efficacy of infrared diode laser for the treatment of posterior retinopathy of prematurity (ROP). METHODS 48 eyes of 25 premature babies (mean birth weight 779 (SD 127.7) g; mean gestational age 25.5 (SD 1.47) weeks) with threshold ROP in zone I and posterior zone II were treated by the indirect infrared (810 nm) diode laser. Confluent burns were applied to the avascular retina. In 18 eyes, an additional row of laser burns was added posterior to the ridge. RESULTS Favourable anatomical results were noted in 41 eyes (85.4%). ROP stage 5 developed in two eyes, ROP stage 4A developed in four eyes, and ROP stage 4B in one eye. Three of the eyes with stage 4A eyes were successfully buckled; the fourth was not operated on and remained demarcated by laser scars. No complications were noted. CONCLUSION In this series, the diode laser was found to be a safe and effective treatment for posterior ROP.

Corneal topographic changes after retinal and vitreous surgery

PURPOSE To investigate the topographic changes in the cornea after retinal and vitreous operations. DESIGN Observational prospective case series. PARTICIPANTS The study population included 46 patients after vitreoretinal surgery: 11 underwent pneumatic retinopexy, 10 underwent vitrectomy, and 25 underwent scleral buckling procedure. METHODS The corneal topography was measured by videokeratography with the absolute program and evaluated statistically by a quantitative comparative method, which was developed for this study, for the whole and the central cornea. MAIN OUTCOME MEASURES The corneal topographic changes were measured in diopters (D), evaluating and comparing the preoperative and postoperative measurements. RESULTS None of the operative procedures changed the shape of the whole cornea. Vitrectomy induced radial steepening of the central cornea 1.2 to 1.6 D, corresponding to the scleral sutures. Central steepening (average, 2.2 D) was also noted in the first week after circular buckling, but it flattened (average, 1.4 D) after 1 to 3 months. When an additional radial or circumferential buckling element was added to the circular buckle, steepening of the entire cornea and radial steepening of the central cornea (average, 0.6-0.8 D) occurred in the first week and flattened or returned to baseline after 1 to 3 months. There was no correlation between the location of the additional buckling element and the corneal topographic change. CONCLUSIONS Corneal videokeratography is a useful tool for evaluating the postoperative corneal curvature. It showed that vitreoretinal surgery alters the shape of the cornea when buckling or scleral sutures are used, but pneumatic retinopexy does not.

Angiographic and flow patterns of retinal choroidal anastomoses in age-related macular degeneration with occult choroidal neovascularization.

OBJECTIVE To identify the angiographic features of retinal choroidal anastomoses (RCAs) in patients with newly diagnosed occult choroidal neovascularization (CNV) in the setting of age-related macular degeneration (AMD) and to determine the sequence of flow between the RCA and the CNV. DESIGN Retrospective cross-sectional study. PARTICIPANTS The angiograms of 205 eyes of 153 consecutive patients with occult CNV on fluorescein angiography (FA) and focal hot spots on indocyanine green angiography (ICGA) were evaluated retrospectively. METHODS OF TESTING: Red-free photographs and sequential digital fluorescein and indocyanine green angiograms obtained by confocal scanning laser ophthalmoscope (the Heidelberg Retina Angiograph; Heidelberg Engineering GmbH, Dossenheim, Germany). MAIN OUTCOME MEASURES The angiograms were evaluated for the presence of RCA. The following angiographic characteristics were recorded: number and type of anastomoses, location, distance from fovea, area of CNV, presence of pigment epithelium detachment (PED), cystoid macular edema on FA, and intraretinal leakage on ICGA. The direction of flow between the RCA and the CNV was identified by analyzing high-speed angiograms. RESULTS Retinal choroidal anastomoses were identified in 57 eyes (28%), in 49 of 154 eyes with PED (32%), and in 8 of 51 eyes without PED (16%). Of 109 anastomoses, 70% were venous and 30% were arterial. Ninety-six percent of the eyes had at least one venous anastomosis, 49% of the eyes had an arterial anastomosis, and 46% of the eyes had both. Cystoid macular edema was seen on FA in 37 eyes (65%), and intraretinal indocyanine green leakage was noted in 52 eyes (91%). Twenty-two eyes that underwent high-speed ICGA were analyzed for the direction of flow. All 15 eyes having arterial and venous anastomoses demonstrated a filling pattern from the retinal arteriole to the CNV, followed by the retinal venule. Seven eyes with venous RCA showed flow sequence from the CNV to the collecting retinal venule. CONCLUSIONS Our study supports the presence of RCA in the early stages of acute exudative AMD with occult CNV, mainly with serous PED. High-speed angiography helps to identify the filling sequence of the RCA and the CNV, and therefore may guide the clinician in planning treatment strategies.

Diode laser treatment of retinopathy of prematurity: anatomical and refractive outcomes.

Purpose: To examine the anatomical and refractive outcomes of infrared diode laser photocoagulation (DLPC) for the treatment of threshold retinopathy of prematurity (ROP). Methods: The charts of all consecutive premature neonates with ROP treated by DLPC at our tertiary center from December 1, 1996, to December 31, 2004, were reviewed. Results: The group included 100 neonates (194 eyes) with a mean birth weight ± SD of 833.9 ± 250.3 g and a mean gestational age ± SD of 26 ± 1.9 weeks. Sixty-two percent of neonates had zone I or posterior zone II ROP. Each eye received a mean ± SD of 1,740 ± 990 laser applications, and 21% of eyes received an additional 1 to 2 rows posterior to the ridge. Neonates treated after December 2003 (cutoff date of the Early Treatment of Retinopathy of Prematurity study) underwent a significantly greater number of laser applications (mean ± SD, 2,286 ± 1,087) than did neonates treated earlier. Anatomical results of laser treatment were favorable for 179 eyes (92.3%) at a mean follow-up ± SD of 33.6 ± 27.2 months. After vitreoretinal surgery, partial or total retinal detachment was documented for 2.5% of patients who received posterior-to-the-ridge laser treatment and 3.8% of patients treated only on the avascular retina. Refractive data were available for 134 eyes: 55.2% had myopia of −5 diopters (31.3%) or greater (23.9%). Strabismus was found in 21 (28.8%) of 73 neonates tested. Gestational age was correlated with corrected age at treatment, zone of ROP, number of laser applications, and spherical equivalent. Snellen visual acuity of 6/12 or more occurred in 17 of 24 patients who complied with testing. Conclusion: DLPC is a safe and effective treatment for ROP. Neonates of lower gestational age and birth weight require earlier and more aggressive laser treatment and may have a higher refractive error.

Role of transesophageal echocardiography in the evaluation of patients with retinal artery occlusion

OBJECTIVE To evaluate the role of transesophageal echocardiography (TEE) in detecting cardiac and thoracic aortic sources of retinal emboli. DESIGN Retrospective observational case series. PARTICIPANTS The study population consisted of 18 patients who were initially seen with retinal artery occlusion (7 central, 11 branch) and underwent TEE as part of the systemic evaluation. INTERVENTION All patients underwent TEE, consisting of complete two-dimensional and Doppler color flow examinations. TEE was done immediately after transthoracic echo (TTE) examination. The medical records were reviewed. MAIN OUTCOME MEASURE Detection of a possible cardiac or thoracic aortic source of retinal embolus. RESULTS Cardiac or thoracic aortic pathologic conditions, which were a possible source of the retinal emboli, were detected by TEE in 13 of the 18 patients (72%). They included aortic arch atheroma (n = 7), mitral annulus calcification (n = 4), left atrial appendage thrombus (n = 2), valvular abnormalities (n = 5), left atrial smoke (n = 3), and patent foramen ovale (n = 3). In 11 patients (61%), at least one cardiac or aortic source of emboli detected by TEE was missed by TTE. Significant carotid artery disease (>or=40% stenosis) was present in 3 of 16 patients (17%). CONCLUSIONS TEE is a potentially useful modality for detecting possible sources of retinal artery emboli and may be considered as an adjunct to the routine evaluation of affected patients.