Maria Lucia Cascavilla

Repeated Intravitreal Dexamethasone Implant (Ozurdex®) for Retinal Vein Occlusion

Purpose: To evaluate the effects of repeated intravitreal dexamethasone implant (IDI) (Ozurdex®) in eyes with macular edema (ME) due to retinal vein occlusion (RVO). Methods: We reviewed the charts of patients with RVO-related ME, who received repeated Ozurdex IDI (0.7 mg) on an ‘as-needed’ basis. Main outcome measures included changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), retreatment interval, and incidence of side effects. Results: A total of 33 eyes were included for analysis. Retreatment with Ozurdex was judged necessary after 4.7 ± 1.1 months from the first IDI (1st IDI) and 5.1 ± 1.5 months from the second IDI (2nd IDI). Baseline BCVA was 0.65 ± 0.43 logMAR; it significantly improved to 0.50 ± 0.42 logMAR after 1.4 ± 0.7 months from the 1st IDI (peaking efficacy) (p < 0.001) and to 0.48 ± 0.44 logMAR after 1.8 ± 0.8 months from the 2nd IDI (peaking efficacy) (p < 0.001). CMT decreased from 636 ± 217 µm (baseline) to 300 ± 114 µm, 1.4 ± 0.7 months after the 1st IDI (p < 0.001), and to 298 ± 91 µm, 1.8 ± 0.8 months after the 2nd IDI (p < 0.001). A rebound effect was recorded in 7 eyes after the 1st IDI (mean 168 ± 158 µm) and in 4 eyes after the 2nd IDI (mean 215 ± 199 µm). All eyes with a rebound effect improved again after a 2nd intravitreal Ozurdex injection. No serious adverse events were observed; 12 eyes developed a transient IOP increase, and cataracts were extracted in 2 eyes. Conclusion: Repeated intravitreal Ozurdex on an ‘as-needed’ basis, with a retreatment interval <6 months, may produce long-term clinically meaningful benefits in the treatment of ME due to RVO, without other significant side effects than expected after intraocular corticosteroid treatment.

Intravitreal ranibizumab versus bevacizumab for treatment of myopic choroidal neovascularization.

Purpose: To compare intravitreal bevacizumab (IVB) and intravitreal ranibizumab (IVR) in the treatment of subfoveal choroidal neovascularization associated with pathologic myopia. Methods: Fifty-five patients fulfilling inclusion and exclusion criteria were randomized either to IVB or to IVR. After the first injection, re-treatments were performed on a pro re nata basis in monthly examinations over an 18-month follow-up. Primary outcome measures were the change in mean best-corrected visual acuity and the proportion of eyes improving in best-corrected visual acuity by >1 and >3 lines at the 18-month examination. Results: Forty-eight eyes received the treatment and were subsequently included in the analysis. At the 18-month examination, a significant improvement of 1.7 lines and 1.8 lines compared with baseline were noticed in the IVR and IVB subgroups, respectively. The difference in the final mean best-corrected visual acuity between the groups was not significant. A 3-line gain or higher was noted in 30% of eyes in the IVR subgroup and 44% of eyes in the IVB subgroup. Although both groups attained a significant improvement in central macular thickness, the IVR subgroup achieved a faster central macular thickness reduction. A significantly lower number of injections were administered in the IVR subgroup (2.5) compared with the IVB subgroup (4.7; P < 0.001). Conclusion: Intravitreal ranibizumab and IVB are effective in the treatment of subfoveal myopic choroidal neovascularization. Intravitreal ranibizumab achieved greater efficacy than IVB in terms of the mean number of injections administered.

Intravitreal dexamethasone implant in patients with persistent diabetic macular edema.

Purpose: To evaluate the effects of a single injection of Ozurdex over 6 months in eyes with persistent diabetic macular edema (DME). Methods: In this retrospective interventional study, 9 patients with decreased visual acuity, as a result of persistent DME, received Ozurdex (intravitreal dexamethasone implant 0.7 mg). Main outcome measures included changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Results: Nine eyes of 9 patients (5 males, 4 females; mean age 58 years) were included in the analysis. The mean duration of DME was 49.9 months (range 24–85). All patients had undergone previous treatments for DME (intravitreal injection of anti-vascular endothelial growth factor, steroids or laser photocoagulation) before entering the study. At baseline, the mean BCVA was 0.74 ± 0.33 logMAR, and the mean CRT was 502 ± 222.16 µm. The mean BCVA was unchanged on the third day (0.74 ± 0.38 logMAR, p = 0.5), improved to 0.62 ± 0.32 logMAR (p = 0.02), 0.59 ± 0.26 logMAR (p = 0.02) and 0.63 ± 0.38 logMAR (p = 0.6) after the first, third and fourth months, respectively, and decreased again to 0.73 ± 0.35 logMAR (p = 0.4) at 6 months. The mean CRT improved to 397 ± 115.31 µm (p = 0.17), 271 ± 99.97 µm (p = 0.007), 325 ± 133.05 µm (p = 0.03) and 462 ± 176.48 µm (p = 0.36) on the third day and after 1, 3 and 4 months of follow-up and then increased again to 537 ± 265.42 µm (p = 0.33) at 6 months. Eight patients needed retreatments in the sixth month. One eye developed a transient intraocular pressure (IOP) increase 1 month after injection, which was successfully managed with topical IOP-lowering medication. Conclusion: In eyes with persistent DME, Ozurdex produces improvement in BCVA and CRT as soon as the first days after the injection. Such improvement is maintained until the fourth month.

Bevacizumab vs Photodynamic Therapy for Choroidal Neovascularization in Multifocal Choroiditis

OBJECTIVE To compare the effectiveness of photodynamic therapy (PDT) vs intravitreal bevacizumab injection in patients with subfoveal choroidal neovascularization (CNV) secondary to multifocal choroiditis (MC). METHODS Patients affected by subfoveal CNV associated with MC referred for clinical evaluation from March 1, 2005, to July 31, 2008, were considered for this pilot randomized clinical trial. Twenty-seven patients were included in the study and followed up from March 15, 2005, through April 30, 2009. After randomization, patients receiving PDT were treated according to the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy protocol, whereas patients receiving intravitreal bevacizumab injection, after a loading phase of 3 monthly injections, were examined monthly and re-treated on the basis of detection of fluid on optical coherence tomography and/or leakage on fluorescein angiography. MAIN OUTCOME MEASURES The primary outcome measure was the 5- and 15-letter change on the Early Treatment of Diabetic Retinopathy Study charts at 12-month examinations compared with baseline. Secondary outcomes included central macular thickness changes. RESULTS Thirteen and 14 patients were randomized to PDT and bevacizumab treatment, respectively. At the 12-month examination, 5 of 14 eyes treated with bevacizumab and 0 of 13 eyes treated with PDT experienced a best-corrected visual acuity gain of greater than 3 lines (P = .04). Twelve eyes in the bevacizumab group and 6 eyes in the PDT group gained more than 1 line (P = .04). The central macular thickness showed a progressive reduction in both subgroups without a significant difference compared with the baseline values. CONCLUSIONS Greater beneficial effects can be achieved using intravitreal bevacizumab injection rather than PDT for the treatment of subfoveal CNV secondary to MC. Larger multicenter investigations are needed to confirm our preliminary results. Application to Clinical Practice Currently, there is no precise indication regarding the best therapeutic approach to subfoveal CNV secondary to MC. This investigation was designed to verify whether intravitreal bevacizumab injection has a more beneficial effect with respect to PDT.

Macular nerve fibre and ganglion cell layer changes in acute Leber's hereditary optic neuropathy

Aims To evaluate longitudinal retinal ganglion cell inner plexiform layer (GC-IPL) and macular retinal nerve fibre layer (mRNFL) thickness changes in acute Lebers hereditary optic neuropathy (LHON). Methods Six eyes of four patients with LHON underwent SD-OCT (optical coherence tomography) at month 1, 3, 6 and 12 after visual loss. In two eyes, the examination was carried out in the presymptomatic stage. The relationship and curves for area under the receiver operator characteristic (AUROC) were generated to assess the ability of each parameter to detect ganglion cell loss. Results Significant longitudinal thinning of GC-IPL and mRNFL was detected in LHON. GC-IPL thinning was detectable in the deviation map during the presymptomatic stage in the inner ring of the nasal sector and then it progressively extended following a centrifugal and spiral pattern. Similarly, mRNFL thinning began in the inferonasal sector and it progressively extended. No further statistically significant changes were detected after month 3. The highest level of AUROC values at 1 month were detected in the nasal sectors and inferonasal mRNFL thickness reached AUROC value=1. All the parameters were equally able to detect ganglion cell loss from month 2 to 12. Conclusions The natural history of GC-IPL thinning follows a specific pattern of reduction, reflecting the anatomical course of papillomacular fibres. Month 6 represents the end of GC-IPL loss. GC-IPL and mRNFL thinning is detectable before onset of visual loss. These observations can help future therapeutic approaches for both LHON carriers at high risk of conversion and patients with acute early LHON.

Impact Of Intravitreal Dexamethasone Implant (ozurdex) On Macular Morphology And Function

Purpose: To investigate the impact of intravitreal dexamethasone implant (Ozurdex) on macular morphology and function in eyes with macular edema secondary to central retinal vein occlusion. Methods: Twelve treatment-naive patients with decreased visual acuity because of central retinal vein occlusion–related macular edema were enrolled in this prospective uncontrolled study. Patients were treated with intravitreal Ozurdex and followed up at 1 month and 3 months for the evaluation of morphologic and functional outcomes, by means of best-corrected visual acuity, microperimetry, multifocal electroretinography, and customized high-resolution enhanced depth imaging spectral-domain optical coherence tomography scans. Results: Twelve eyes of 12 patients (10 men, 2 women; mean age 56.2 ± 13.0 years) were included for analysis. At 1 month, mean best-corrected visual acuity, retinal sensitivity (microperimetry), multifocal electroretinography parameters, central macular thickness, and specific neurosensorial retinal measurements improved significantly. We found a significant negative correlation between retinal sensitivity and central macular thickness at 1 month and 3 months (r = −0.831, P = 0.001; r = −0.881, P = 0.001; respectively). Moreover, retinal sensitivity was negatively related to both outer and inner retinal thickness in all four intervals from the fovea. From baseline to Month 1, change in outer retinal thickness was positively related to multifocal electroretinography N1R1 amplitude change (r = 0.698, P = 0.012), whereas change in central macular thickness was negatively related to multifocal electroretinography P1R1 amplitude change (r = −0.701, P = 0.011). At 3 months, improvement of mean retinal sensitivity and central macular thickness slightly decreased. Conclusion: In eyes with macular edema secondary to central retinal vein occlusion, intravitreal dexamethasone provides functional benefits that correlate well with ultrastructural macular changes.

Fluorescein angiography and spectral-domain optical coherence tomography for monitoring anti-VEGF therapy in myopic choroidal neovascularization.

Aim: To evaluate the agreement between fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT) in detecting myopic choroidal neovascularization (CNV) activity during bevacizumab treatment. Methods: Thirty-four patients with subfoveal myopic CNV were prospectively enrolled. FA and SD-OCT were performed at baseline and at all planned monthly visits. After the first injection, additional treatments were administered following detection of fluid on SD-OCT and/or leakage on FA. κ-Analysis was performed to examine the agreement between FA and SD-OCT. Results: At baseline, FA and SD-OCT agreed in 26/34 cases (κ = 0.23); sensitivity and specificity were 77.4 and 66.7%, respectively. Seven eyes presented leakage on FA with no fluid on SD-OCT, 1 case showed intraretinal fluid on SD-OCT and no leakage on FA. At the 1-month examination, specificity and κ-value improved, and 30/34 cases showed complete concordance. At the 3- and 4-month examinations, a discordance was noted in 6 cases. From the 5-month examination on, a correspondence was achieved in at least 30/34 cases and reached a perfect match in 11 sessions. Conclusions: Our study confirms the key role of FA in diagnosing myopic CNV. It seems possible there may be a role for SD-OCT in assisting FA to monitor the myopic CNV activity during anti-vascular endothelial growth factor antibody treatment.

Ranibizumab in the treatment of patients with visual impairment due to diabetic macular edema

Diabetic macular edema is the major cause of visual acuity impairment in diabetic patients. The exact etiopathogenesis is unknown and, currently, grid/focal retinal laser photocoagulation represents the recommended treatment. It has been demonstrated that vascular endothelial growth factor (VEGF) plays a key role in the pathogenesis of diabetic macular edema by mediating vascular permeability and accumulation of intracellular and extracellular fluid, and thereby represents an appealing candidate as a therapeutic target for the treatment of diabetic macular edema. The advent of intravitreal anti-VEGF drugs has opened up a new era for the management of diabetic macular edema. At present, three anti-VEGF substances are available for routine clinical use, ie, pegaptanib, ranibizumab, and bevacizumab. The aim of this review is to summarize the evidence supporting the use of ranibizumab in clinical practice. Most of the studies analyzed in this review are prospective, controlled clinical trials that have focused on documenting the therapeutic effect of ranibizumab and its safety, providing encouraging results.

Intravitreal bevacizumab for extrafoveal choroidal neovascularization secondary to pathologic myopia.

Purpose: To assess the effects of intravitreal bevacizumab injections in the treatment of extrafoveal choroidal neovascularization (CNV) associated with pathologic myopia. Methods: Patients diagnosed with pathologic myopia complicated by extrafoveal CNV were considered in this prospective, open-label interventional study. All patients underwent a complete ophthalmologic examination, including Early Treatment Early of Diabetic Retinopathy Study (ETDRS) visual acuity measurement, optical coherence tomography, and fluorescein angiography. The protocol treatment included a first injection, followed by repeated injections over a 24-month follow-up period on the basis of optical coherence tomography and angiographic features, monitored monthly. Primary outcomes were the mean changes in best-corrected visual acuity and the proportion of eyes gaining at least 15 letters at the 24-month examination. Secondary outcomes included central macular thickness, size of the CNV, and extension to the fovea. Results: Fifteen patients were included in the study. Mean best-corrected visual acuity changed from 0.47 logarithm of the minimum angle of resolution (20/60 Snellen equivalent) at baseline to 0.22 logarithm of the minimum angle of resolution (20/30 Snellen equivalent) at the 24-month examination. An improvement of at least 3 ETDRS lines was achieved by 7 eyes (46.6%) at the 24-month examination. Mean central macular thickness changed from 313 &mgr;m to 254 &mgr;m at the 24-month examination (P = 0.008). Mean CNV size decreased from 348 &mgr;m2 to 251 &mgr;m2 at 24 months (P = 0.029). Conclusion: Intravitreal bevacizumab injection is a beneficial treatment for extrafoveal CNV associated with pathologic myopia.

Prospective Evaluation of Morphological and Functional Changes after Repeated Intravitreal Dexamethasone Implant (Ozurdex®) for Retinal Vein Occlusion

Aims: To evaluate changes in macular morphology and function after repeated intravitreal dexamethasone implant (Ozurdex®) for macular edema (ME) due to retinal vein occlusion (RVO). Methods: Consecutive treatment-naïve patients with ME secondary to RVO were treated with Ozurdex and followed up to 12 months to evaluate functional and morphological outcomes by means of best-corrected visual acuity (BCVA) and microperimetry and by enhanced depth imaging optical coherence tomography, respectively. Results: Thirty-five eyes of 35 patients were included for the analysis (26 central RVO, 9 branch RVO). During the 12-month study period, 8 of the 35 eyes (23%) underwent 1 intravitreal dexamethasone implant, 13 of the 35 eyes (37%) underwent 2, and 14 of the 35 eyes (40%) underwent 3 intravitreal dexamethasone implants. At 1 month from the 1st intravitreal dexamethasone implant, the mean BCVA, retinal sensitivity and central macular thickness (CMT) significantly improved compared to the baseline values. At 3 months, the mean BCVA improvement was no more significant, while retinal sensitivity further improved and CMT slightly worsened, remaining, however, significantly better than at baseline. At 12 months, those eyes that had undergone 2 retreatments showed a significant improvement of the mean BCVA, mean retinal sensitivity and CMT compared to the baseline values [0.61 ± 0.29 logarithm of the minimum angle of resolution (LogMAR) vs. 0.82 ± 0.33 LogMAR, p = 0.011; 12.94 ± 4.73 dB vs. 10.75 ± 3.27 dB, p = 0.043, and 321 ± 91 µm vs. 735 ± 169 µm, p = 0.001, respectively]. In those eyes that had undergone only 1 retreatment, a significant improvement was recorded only for the CMT (500 ± 224 µm vs. 695 ± 302 µm, p = 0.044). The mean retreatment interval between the 1st and the 2nd injection was 4.5 ± 1.1 months (range 3-7 months), and between the 2nd and the 3rd injection it was 4.1 ± 1 months (range 3-6 months). Conclusions: In eyes with ME secondary to RVO, Ozurdex produces functional benefits as early as 1 month after treatment/retreatment. Current optical coherence tomography and microperimetry findings confirm the concept that, in most cases, the optimum retreatment interval should be <6 months from the 1st injection.