Michael Georgopoulos

INTRAVITREAL BEVACIZUMAB (AVASTIN) FOR MACULAR OEDEMA SECONDARY TO RETINAL VEIN OCCLUSION: 12-MONTH RESULTS OF A PROSPECTIVE CLINICAL TRIAL

Aims: The aim of the study was to evaluate functional and anatomical changes after intravitreal bevacizumab (Avastin®) in eyes with persistent macular oedema secondary to branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO). Methods: Twenty-nine consecutive eyes with macular oedema secondary to BRVO (21 eyes) or CRVO (eight eyes) were included in a prospective clinical trial. Eyes were treated with three initial intravitreal bevacizumab injections of 1 mg at a monthly interval. Retreatment was based on central retinal thickness (CRT) based on optical coherence tomography. If continuous injections were indicated up to month 6, the dose was increased to 2.5 mg. Results: After 12 months of follow-up, mean visual acuity increased from 50 letters (20/100) at baseline to 66 letters (20/50+1; +16 letters; p<0.001) at month 12 and CRT decreased from 558 μm at baseline to 309 μm at month 12 (−249 μm; p<0.001). Patients received a mean of eight out of 13 possible injections. No drug-related systemic or ocular side effects following intravitreal bevacizumab treatment were observed. Fluorescein angiography revealed no progression of avascular areas. Conclusions: Intravitreal therapy using bevacizumab appears to be a safe and effective treatment in patients with macular oedema secondary to retinal vein occlusion. However, the main limitations of this treatment modality are its short-term effectiveness and high recurrence rate.

The capsular tension ring: designs, applications, and techniques

&NA; Originally, the open poly(methyl methacrylate) (PMMA) capsular tension ring (CTR) was designed to compensate for zonular defects or to stretch the posterior capsule in highly myopic eyes not receiving an intraocular lens (IOL). We address the variety of subsequent designs, applications, and techniques that have evolved. With pre‐existing or intraoperative zonular defects, a standard CTR may be inserted before or at any time during cataract removal to maintain or re‐establish an extended capsular diaphragm. For profound zonular dialysis or weakness, a CTR was designed for scleral fixation. Capsular tension rings with integrated tinted sector shields have been developed to compensate for sector iris colobomas or aniridia. The CTR has also been used as a measuring gauge for in vivo quantification of capsule dimensions and postoperative capsular shrinkage. The CTR has improved control during primary posterior capsulorhexis and prevented oval distortion along the lens axis postoperatively. During combined cataract and vitreous surgery, a CTR prevents capsule damage and provides undisturbed peripheral visualization before IOL implantation. Capsular tension rings may also influence capsule opacification formation. A special band‐shaped CTR with sharp edges was developed to inhibit lens epithelial cell migration and avoid capsulorhexis–optic contact.

Intravitreal Avastin for macular oedema secondary to retinal vein occlusion: a prospective study

Objective: To evaluate efficacy and safety of intravitreal bevacizumab (Avastin) in eyes with macular oedema secondary to central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO). Methods: Twenty-eight consecutive patients (28 patients, 29 eyes, 8 CRVO, 21 BRVO) were enrolled in the study. Three intravitreal injections of 1 mg bevacizumab (0.04 ml) were administered at 4-week intervals; further retreatment was based on optical coherence tomography (OCT) findings. Follow-up examinations were done at days 1, 7 and 28 and at monthly intervals thereafter. Results: Mean baseline central retinal thickness (CRT) in OCT was 558 µm (range 353–928 µm) and mean BCVA was 20/100. One day after the first injection, CRT significantly decreased to 401 μm (p<0.01). Three injections reduced macular oedema to 328 μm CRT (p<0.01) and improved BCVA to 20/50 (p<0.01). At 6 months, CRT was 382 μm (p<0.01), and BCVA was stable at 20/50−2 (p<0.01), FA showed no evidence of increased avascular zones. Conclusion: Intravitreal injections of bevacizumab appear to be a safe and effective therapy in the treatment of macular oedema secondary to retinal vein occlusion.

Intraocular concentrations of growth factors and cytokines in retinal vein occlusion and the effect of therapy with bevacizumab.

PURPOSE To investigate concentrations of growth factors and inflammatory cytokines in eyes with central (CRVO) and branch (BRVO) retinal vein occlusion before and during therapy with bevacizumab and to identify associations with disease activity. METHODS In a prospective clinical trial, 13 eyes of patients with CRVO (n = 5) or BRVO (n = 8) were included. Bevacizumab was administered intravitreously at baseline and months 1 and 2. Retreatments were given at monthly visits if OCT showed edema or when vision loss occurred. Aqueous humor samples were taken each time injections were performed. Follow-up was 15 months. Samples from patients with cataract served as the control. Multiplex bead assays were used for measurement of 28 growth factors and cytokines. RESULTS During therapy with bevacizumab, VEGF levels were reduced to below detection in the first 2 months. Whenever criteria for retreatment were met, VEGF was measurable again. The decrease in VEGF was associated with a decrease in central retinal thickness (CRT) and improvement in visual acuity (VA). Significantly increased concentrations of VEGF, IL-6, IL-8, IP-10, MCP-1, and PDGF-AA were observed in aqueous humor samples of patients with CRVO compared with the control samples. CONCLUSIONS VEGF levels were significantly elevated in patients with CRVO compared with control subjects. Intravitreal injections of bevacizumab resulted in a substantial decrease of VEGF under physiologic levels and remained low under the loading dose of three consecutive monthly retreatments. Macular edema was related to VEGF levels in the aqueous humor.

Neovascular Age-related Macular Degeneration: Intraocular Cytokines and Growth Factors and the Influence of Therapy with Ranibizumab

PURPOSE To investigate concentrations of growth factors and inflammatory cytokines in eyes with neovascular age-related macular degeneration (AMD) before and during therapy with intravitreal ranibizumab and to identify associations with disease activity. DESIGN Prospective clinical trial. PARTICIPANTS AND CONTROLS Twenty-eight eyes of patients with neovascular AMD were compared with 28 eyes of age-matched patients with cataract as control. METHODS Ranibizumab was administered intravitreously once at baseline, and retreatments were given at monthly visits if optical coherence tomography (OCT) revealed macular edema or vision loss had occurred. Aqueous humor samples were taken each time intravitreal interventions were performed. Follow-up was 12 months. Luminex (Luminex Inc., Austin, TX) multiplex assays were used for measurement of 29 different growth factors and cytokines, including vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). MAIN OUTCOME MEASURES Differences in the concentrations of growth factors and inflammatory cytokines in eyes with neovascular AMD compared with control eyes and the influence of therapy with intravitreal ranibizumab. RESULTS A significantly increased expression of VEGF (P = 0.033) and a significantly decreased expression of PDGF (P = 0.038) were measured in the aqueous humor of eyes with neovascular AMD. Furthermore, a significant decrease of VEGF (P<0.001) was observed after intravitreal injection of ranibizumab along with significant changes in visual acuity and central retinal thickness (P = 0.039 and P<0.001). During follow-up with a flexible regimen, a correlation was identified between increased VEGF levels and persistent or recurrent macular edema. Changes in PDGF levels were strongly associated with alterations in VEGF concentration. CONCLUSIONS Vascular endothelial growth factor and PDGF-AA seemed to be associated with disease activity of neovascular AMD. Intravitreal anti-angiogenic treatment with ranibizumab resulted in significantly decreased intraocular VEGF expression below physiologic levels compared with controls. This effect was measurable as long as 4 weeks after each injection and was prolonged by consecutive retreatment. With recurrence after discontinuation of treatment, VEGF levels increased again.

Comparison of 4 methods for quantifying posterior capsule opacification.

Purpose: To compare the results of posterior capsule opacification (PCO) quantification and the repeatability of a fully automated analysis system (Automated Quantification of After‐Cataract [AQUA]) with that of 2 other quantification methods and subjective grading of PCO. A test set of digital retroillumination images of 100 eyes with PCO of varying degrees was used. Setting: Department of Ophthalmology, University of Vienna, Vienna, Austria. Methods: One hundred digital retroillumination images of eyes (100 patients) with PCO were selected to attain an even distribution from mild to severe cases. The images were evaluated by 4 methods: subjective grading by 4 experienced and 4 inexperienced examiners, the subjective Evaluation of Posterior Capsular Opacification (EPCO) system, posterior capsule opacification (POCO) software, and the AQUA system. Ten images were presented twice to assess the reproducibility of the analysis systems. Results: Subjective grading correlated best with the subjective EPCO system and the objective AQUA system (r = 0.94 and r = 0.93, respectively). The POCO system showed very early saturation and therefore a much weaker correlation (r = 0.73). The POCO scores reached the maximum of 100% in several minimal to mild PCO cases. The reproducibility of the AQUA software was perfect and that of the other analysis systems, comparably satisfactory. Conclusion: The objective AQUA score correlated well with subjective methods including the EPCO system. The POCO system, which assesses PCO area, did not adequately describe PCO intensity and includes a subjective step in the analysis process. The AQUA system could become an important tool for randomized masked trials of PCO inhibition.

Effect of a silicone intraocular lens with a sharp posterior optic edge on posterior capsule opacification

Purpose: To compare the inhibiting effect on posterior capsule opacification (PCO) of a silicone intraocular lens (IOL) with a sharp posterior optic edge (ClariFlex OptiEdge®, Advanced Medical Optics) and a silicone IOL with a round optic edge (PhacoFlex SI‐40, Advanced Medical Optics). Setting: Department of Ophthalmology, University of Vienna, Vienna, Austria. Methods: This prospective randomized patient‐ and examiner‐masked study comprised 104 eyes of 52 patients with bilateral age‐related cataract. All patients had cataract surgery in both eyes and received a sharp‐edged IOL in 1 eye and a round‐edged IOL in the other eye. Postoperative examinations were at 1 week, 1 and 6 months, and 1 year. Digital slitlamp and retroillumination images were taken of each eye. The amount of PCO was assessed subjectively at the slitlamp and objectively using Automated Quantification of After‐Cataract (AQUA) automated‐image analysis software. Results: The sharp‐edged IOL group had significantly less regeneratory and fibrotic PCO 1 month, 6 months, and 1 year after surgery. The mean AQUA PCO score (scale 0 to 10) was 0.71 in the sharp‐edged IOL group and 1.40 in the round‐edged IOL group (P<.001). The sharp‐edged IOL group had less peripheral fibrotic PCO. There was no significant difference between the 2 IOL groups in patient reports of edge glare. Conclusion: The sharp‐edged design of the ClariFlex OptiEdge silicone IOL led to significantly less PCO than the round‐edged PhacoFlex SI‐40 IOL 1 year postoperatively.

Local tumor control and morbidity after one to three fractions of stereotactic external beam irradiation for uveal melanoma

BACKGROUND AND PURPOSE To evaluate prospectively local tumor control and morbidity after 1-3 fractions of stereotactic external beam irradiation (SEBI) in patients with uveal melanoma, unsuitable for ruthenium-106 brachytherapy or local resection. MATERIAL AND METHODS This phase I/II study includes 62 selected patients with uveal melanoma. The mean initial tumor height was 7.8+/-2.8 mm. With the Leskell gamma knife SEBI, 41 patients (66%) were irradiated with two equal fractions of 35, 30 or 25 Gy/fraction, 14 patients (22%) were treated with three fractions of 15 Gy each, and seven patients (11%) with small tumor volumes below 400 mm(3) were treated with one fraction of 45 Gy. The mean total dose was 54+/-8 Gy. The minimal follow-up period was 12 months, and the median follow-up was 28.3 months. Data on radiation-induced side-effects were analyzed with the Cox proportional hazards model for possible risk factors. RESULTS Local tumor control was achieved in 98% and tumor height reduction in 97%. The mean relative tumor volume reductions were 44, 60 and 72% after 12, 24 and 36 months, respectively. Seven patients developed metastases (11%). Secondary enucleation was performed in eight eyes (13%). Morbidity was significant in tumors exceeding 8 mm in initial height; it was comparable and acceptable in those smaller. In the stepwise multiple Cox model, tumor localization, height and volume, planning target volume (PTV), total dose and patient age were identified as the strongest risk factors for radiation-induced lens opacities, secondary glaucoma, uveitis, eyelash loss and exudative retinal detachment. In this model, the high-dose volume irradiated with more than 10 Gy/fraction was the strongest risk factor for radiation-induced uveitis. CONCLUSIONS Stereotactic external photon beam irradiation and a total dose of 45-70 Gy delivered in one to three fractions are highly effective at achieving local tumor control in uveal melanoma. Further clinical studies using smaller fraction doses, and consequent smaller high-dose volumes, are justified to optimize dose and fractionation. Fractionated stereotactic irradiation has a challenging potential as an eye-preserving treatment in uveal melanoma.

Assessment of optic disk blood flow in patients with open-angle glaucoma

PURPOSE To characterize optic disk blood flow in patients with open-angle glaucoma compared with age-matched healthy control subjects. METHODS In this prospective cross-sectional study, 90 eyes of 90 patients with open-angle glaucoma and 61 eyes of 61 age-matched healthy control subjects were evaluated. Flow in the optic disk cup and the neuroretinal rim were assessed with scanning laser Doppler flowmetry. Fundus pulsation amplitude in the cup and the macula were assessed with laser interferometry. Visual field mean deviation was measured with the Humphrey 30 to 2 program. RESULTS Flow in the neuroretinal rim (-18%, P =.002), and in the cup (-46%, P <.001) and fundus pulsation amplitude in the cup (-33%, P <.001) and in the macula (-24%, P <.001) were significantly lower in patients with open-angle glaucoma compared with healthy control subjects. A significant association between blood flow measurements in the cup and fundus pulsation amplitudes in the cup was observed in both study cohorts. A significant association was also observed between the mean defect from visual field testing and ocular hemodynamic parameters. CONCLUSIONS Reduced optic disk perfusion in patients with open-angle glaucoma is evidenced from two independent methods in the present study. Moreover, our data indicate that reduced ocular blood flow in these patients is linked to visual field changes. It remains to be established whether compromised optic disk and choroidal blood flow contributes to optic disk damage in glaucomatous eyes or is a secondary functional phenomenon.

Intraocular lens movement caused by ciliary muscle contraction

Purpose: To investigate intraocular lens (IOL) movement, measured as a change in anterior chamber depth (ACD) caused by pilocarpine‐induced ciliary muscle contraction. Setting: Department of Ophthalmology, University of Vienna, Vienna, Austria. Methods: In this prospective study, the ACD was measured using high‐precision, high‐resolution, dual‐beam partial coherence interferometry in 62 pseudophakic eyes of 55 patients under pilocarpine‐ and cyclopentolate‐induced ciliary muscle contraction and relaxation. The following were studied: 2 models of a ring‐haptic IOL (designed to accommodate), a plate‐haptic IOL, and 3 types of 3‐piece IOLs. Measurements were performed 3 months after surgery. Results: The ring‐haptic IOLs and plate‐haptic IOL showed a forward movement (ring haptic 43A, −116 &mgr;m; ring haptic 43E, −222 &mgr;m; plate haptic −162 &mgr;m). The 3‐piece IOLs showed no change in ACD except in 1 IOL type in which there was backward movement (156 &mgr;m). Conclusions: Pilocarpine‐induced ciliary muscle contraction caused forward movement of ring‐ and plate‐haptic IOLs that resulted in an estimated accommodative amplitude of less than 0.50 diopter in most cases. The accommodating ring‐haptic IOLs did not perform better than the conventional plate‐haptic IOL.