Adiel Barak

Electrophysiologic and retinal penetration studies following intravitreal injection of bevacizumab (Avastin).

Purpose: Intravitreal bevacizumab (Avastin; Genentech Inc., San Francisco, CA) is a new treatment for age-related macular degeneration. The aim of this study was to evaluate retinal penetration and toxicity of bevacizumab. Methods: Ten albino rabbits were injected intravitreally with 0.1 mL (2.5 mg) of Avastin into one eye and 0.1 mL saline into the fellow eye. The electroretinogram (ERG) was recorded after 3 hours, 3 days, and 1, 2, and 4 weeks. The visual evoked potential (VEP) was recorded after 4 weeks. Confocal immunohistochemistry was used to assess retinal penetration. Results: The ERG responses of the control and experimental eyes were similar in amplitude and pattern throughout the follow-up period. The flash VEP responses of the experimental eyes were of normal pattern and amplitude and did not differ from those recorded by stimulation of the control eye alone. Full thickness retinal penetration was present at 24 hours and was essentially absent at 4 weeks. Conclusions: Bevacizumab was found to be nontoxic to the retina of rabbits based on electrophysiologic studies. Full thickness retinal penetration may explain observed clinical effects of intravitreal bevacizumab. Although it is difficult to directly extrapolate to humans, our study supports the safe use of intravitreal bevacizumab injection.

Reduced retinal blood flow velocity in diabetic retinopathy.

Purpose: The purpose of this study was to compare the retinal blood flow velocities of patients with diabetes and healthy control subjects. We used a novel device offering a noninvasive diagnostic of retinal function. Methods: Flow velocities in retinal arterioles and venules were quantitatively analyzed by retinal function imager scanning in 58 eyes of 42 patients with nonproliferative diabetic retinopathy and 51 eyes of 32 normal subjects. Group differences were assessed by the mixed-model effect. Results: Average velocity in arterial compartments (in mm/s) was 3.74 ± 1.09 for the diabetic group and 4.19 ± 0.99 for the control subjects. The average velocity of all segments, taking associated heart rate and individual segment widths into account, was 17% slower in the diabetic group (P < 0.0001). In both groups, average venous compartment velocity was lower than the arterial velocity (2.61 ± 0.65 for the diabetic group; 3.03 ± 0.59 for the control subjects). Individual vein velocities, taking heart rate and segment widths into account, was 17% slower, on average, in the diabetic group (P < 0.0001). Conclusion: Our measurement showed significantly decreased flow velocities in the retinal arterioles and venules of patients with diabetes compared with healthy control subjects, supporting the view of abnormal vessel function in eyes with nonproliferative diabetic retinopathy.

Retinal pigment epithelial tear following photodynamic therapy for choroidal neovascularization secondary to AMD.

PurposeTo describe retinal pigment epithelial tear following photodynamic therapy (PDT) for subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).DesignRetrospective interventional case series.MethodsA retrospective study in an institutional practice. We describe seven cases of retinal pigment epithelial (RPE) tear, which developed in seven eyes of seven patients following PDT. All eyes had subfoveal CNV secondary to AMD.ResultsSix eyes had occult subfoveal CNV, and one eye had recurrent classic subfoveal CNV. In five patients, the eye that developed the tear was the second eye, whereas the first eye had a disciform scar. In four eyes, the RPE tear developed after one PDT, in one eye the RPE tear developed after the second PDT, and in two eyes the RPE tear developed after the third PDT. In five of seven cases, there was a significant visual deterioration following the RPE tear.ConclusionsRPE tear is a complication that may occur following PDT in particular when the PDT is applied to an occult subfoveal CNV.

REMOVAL OF SILICONE OIL IN THE MANAGEMENT OF GLAUCOMA IN EYES WITH EMULSIFIED SILICONE

Glaucoma and emulsification are two complications of silicone oil injection that are often coexisting. This study was undertaken to determine whether removal of emulsified oil has any effect on the management of the glaucoma. A comparison of eyes with and without glaucoma with emulsified oil also was undertaken. Eighteen eyes that underwent removal of emulsified silicone oil more than 6 months after the injection of the oil were reviewed. All eyes were observed for at least 6 months after removal with attached retinas. Eleven eyes had glaucoma at the time of removal. The diagnosis of glaucoma preceded the identification of emulsification in 8 of 11 eyes (73%). Removal of the emulsified oil did not affect the intraocular pressure (IOP) in 10 of the 11 (91%) glaucomatous eyes. The IOP was reduced in one patient. In the glaucoma patients, the final visual acuity was significantly reduced compared with the best corrected visual acuity obtained during the follow-up period (P = 0.016). In the nonglaucoma eyes with emulsified oil, the visual acuity did not significantly deteriorate during follow-up. At the end of the follow-up period, optic atrophy was observed in 9 of 11 (82%) of the eyes with glaucoma compared with two of seven (28%) of eyes without glaucoma. The results suggest that removal of emulsified silicone oil failed to control the glaucoma, and could not change the aggressive nature of the glaucoma in these eyes.

Epimacular brachytherapy for neovascular age-related macular degeneration: a randomized, controlled trial (CABERNET).

PURPOSE To evaluate the safety and efficacy of epimacular brachytherapy (EMBT) for the treatment of neovascular age-related macular degeneration (AMD). DESIGN Multicenter, randomized, active-controlled, phase III clinical trial. PARTICIPANTS Four hundred ninety-four participants with treatment-naïve neovascular AMD. METHODS Participants with classic, minimally classic, and occult lesions were randomized in a 2:1 ratio to EMBT or a ranibizumab monotherapy control arm. The EMBT arm received 2 mandated, monthly loading injections of 0.5 mg ranibizumab. The control arm received 3 mandated, monthly loading injections of ranibizumab then quarterly injections. Both arms also received monthly as needed (pro re nata) retreatment. MAIN OUTCOME MEASURES The proportion of participants losing fewer than 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters from baseline visual acuity (VA) and the proportion gaining more than 15 ETDRS letters from baseline VA. RESULTS At 24 months, 77% of the EMBT group and 90% of the control group lost fewer than 15 letters. This difference did not meet the prespecified 10% noninferiority margin. This end point was noninferior using a 20% margin and a 95% confidence interval for the group as a whole and for classic and minimally classic lesions, but not for occult lesions. The EMBT did not meet the superiority end point for the proportion of participants gaining more than 15 letters (16% for the EMBT group vs. 26% for the control group): this difference was statistically significant (favoring controls) for occult lesions, but not for predominantly classic and minimally classic lesions. Mean VA change was -2.5 letters in the EMBT arm and +4.4 letters in the control arm. Participants in the EMBT arm received a mean of 6.2 ranibizumab injections versus 10.4 in the control arm. At least 1 serious adverse event occurred in 54% of the EMBT arm, most commonly postvitrectomy cataract, versus 18% in the control arm. Mild, nonproliferative radiation retinopathy occurred in 3% of the EMBT participants, but no case was vision threatening. CONCLUSIONS The 2-year efficacy data do not support the routine use of EMBT for treatment-naïve wet AMD, despite an acceptable safety profile. Further safety review is required.

Increased retinal blood flow velocity in patients with early diabetes mellitus.

Purpose: To compare retinal blood flow velocity in small vessels of patients with early diabetes mellitus (DM), without any morphologic changes related to diabetic retinopathy, with that in a control group. Methods: The authors used the retinal function imager to measure blood flow velocities, from many small vessels, simultaneously. Twenty-three eyes of 14 patients with early DM and 51 eyes of 31 healthy subjects were enrolled. Differences between the patients and the control group were assessed by mixed linear models. Results: Venous average velocity significantly increased in the DM group (3.8 ± 1.2 vs. 2.9 ± 0.5 mm/second, P < 0.0001) than in the healthy subjects. Arterial velocity of DM patients was also significantly higher (4.7 ± 1.7 vs. 4.1 ± 0.9 mm/second, P = 0.03). There was no statistically significant difference between groups in age, gender, heart rate, and systolic blood pressure. The diastolic blood pressure in the DM patients was lower than that in the healthy group (P = 0.03). Conclusion: There was an increase in arterial and venous retinal blood flow velocities of patients with early DM with no diabetic retinopathy. These findings support the notion that abnormalities in vessel function exist in diabetic eyes before the development of structural changes. This noninvasive approach facilitated the assessment of early hemodynamic abnormalities and may assist in screening and monitoring.

Long-term evaluation of patients treated with dexamethasone intravitreal implant for macular edema due to retinal vein occlusion

PurposeTo evaluate the long-term visual prognosis and complications of patients who received intravitreal Ozurdex injections for the treatment of macular edema (ME) due to retinal vein occlusion (RVO).MethodsA total of 17 patients who received Ozurdex injections in our institution as part of the GENEVA study were recalled for examination. Recorded parameters included final visual acuity (VA), final retinal thickness by optical coherence tomography, persistence of ME, and the occurrence of any complications.ResultsMean follow-up time was 50.5 months. Patients with branch RVO (BRVO) had a more favorable prognosis than central RVO (CRVO), and their mean VA had improved significantly, whereas the mean VA for the patients with CRVO did not improve significantly. Retinal thickness had reduced significantly in the whole group and in each subgroup separately. Complications included 10 patients with cataract progression, 1 with elevated intraocular pressure, and 1 with neovascularization and vitreous hemorrhage.ConclusionsThis is the first reported long-term evaluation of patients treated with Ozurdex. Our results indicate that it has favorable long-term safety profile, and may have a beneficial effect on the visual prognosis in BRVO even in the absence of continuous treatment. Further research is required to establish the optimal retreatment schedule for Ozurdex.

Clinical characteristics of endophthalmitis after an injection of intravitreal antivascular endothelial growth factor.

Purpose: The purpose of this study was to describe the clinical characteristics and management of patients with bacterial endophthalmitis after an intravitreal antivascular endothelial growth factor injection. Methods: This is a retrospective chart review of all patients admitted with suspected endophthalmitis from 2006 to 2008. Results: Endophthalmitis was verified by positive Gram stain and culture in nine eyes. The mean preinjection visual acuity of the 9 eyes was 0.02 ± 0.021 diopters (decimal visual acuity scale) and dropped to 0.01667 ± 0.02449 diopters in the eyes with endophthalmitis. All nine patients presented with reduced visual acuity, of whom seven also had ocular pain. Initial treatment was administered without delay and consisted of vitreous tap and intravitreal antibiotics injection in five cases and pars plana vitrectomy with intravitreal antibiotics injection in the other four cases. Vitreous tap failed in one case. Seven patients underwent a second procedure and two underwent a third procedure. The mean posttreatment visual acuity in all 9 eyes improved significantly (0.19 ± 0.24, P = 0.0071). Five patients had major complications (e.g., retinal detachment, phacolytic glaucoma, and recurrent endophthalmitis). Conclusion: Acute endophthalmitis following anti-VEGF injection appears within days and can result in severe loss of vision if not treated promptly. In our series the clinical and prognostic characteristics were considerably different between culture positive endophthalmitis cases and culture negative cases.

Transcanalicular laser-assisted dacryocystorhinostomy

BACKGROUND AND OBJECTIVE Current techniques of laser-assisted dacryocystorhinostomy are mostly endonasal. In this report, the authors describe their technique of laser-assisted dacryocystorhinostomy performed through the canaliculi and the surgical results they achieved. PATIENTS AND METHODS Fourteen patients with nasolacrimal duct obstruction underwent transcanalicular laser-assisted dacryocystorhinostomy. The bony ostium was perforated using a fiber optic-transmitting, giant-pulse Nd:YAG laser, with an energy of 0.5 to 4 J per pulse. The total energy used to create an ostium was 18 to 34 J. A silicone tube was inserted through the canaliculi and the ostium into the nasal cavity and kept in place for 5 to 7 months. Patients were observed for 18 to 22 months. RESULTS Nine of the 14 patients (64%) reported the disappearance of epiphora following surgery. In 3 patients, no relief of epiphora was obtained. In 1 patient the operation was not completed because of severe nasal bleeding. In another, tearing began 12 months after surgery (6 months after tube removal). CONCLUSIONS Transcanalicular laser-assisted dacryocystorhinostomy is a potentially useful method for performing dacryocystorhinostomy. Technical modifications and improvements are needed to increase the success rate.

Comparison of Pars Plana Vitrectomy With and Without Scleral Buckle for the Repair of Primary Rhegmatogenous Retinal Detachment

PURPOSE To compare pars plana vitrectomy (PPV) with combined PPV and scleral buckle (SB) for the repair of noncomplex primary rhegmatogenous retinal detachment (RRD). DESIGN Retrospective, nonrandomized, interventional case series. METHODS We reviewed 181 consecutive cases of vitrectomy for primary RRD at 2 major medical centers in Israel. The follow-up was at least 3 months. There were 96 eyes in the PPV group and 85 eyes in the PPV plus SB group. Main outcome measures were single-surgery anatomic success (SSAS) and final visual acuity (VA). RESULTS SSAS was achieved in 81.3% and 87.1% in the PPV and PPV plus SB groups, respectively (P=.29). Final anatomic success rate was 98.9% and 98.8%, respectively (P=.61). Final VA was 0.41 (20/51) in the PPV group and 0.53 (20/68) in the PPV plus SB group (P=.13). The final VA was significantly better than the preoperative VA in both groups (P<.0001). In detachments caused by inferior tears, SSAS rates were 80.9% and 81.5% in the PPV and PPV plus SB groups, respectively (P=.74). In phakic eyes, SSAS rates were 92% and 87.5%, respectively, and in pseudophakic eyes, SSAS rates were 77.5% and 86.7%, respectively, in the PPV and PPV plus SB groups (P=.29). CONCLUSIONS The reattachment rate and the final VA were similar in both groups. The addition of SB did not improve the results and was associated with slightly lower VA than with PPV alone. Tear location or lens status had no significant effect on success rates. It is likely that in eyes undergoing PPV for primary RRD, addition of a SB is not warranted.