Maria Douvali

Photodynamic Therapy, Ranibizumab, And Ranibizumab With Photodynamic Therapy For The Treatment Of Polypoidal Choroidal Vasculopathy

Purpose: The purpose of this study was to compare photodynamic therapy (PDT), ranibizumab, and ranibizumab with PDT in polypoidal choroidal vasculopathy. Methods: In this retrospective comparative study, 30 eyes of 30 patients with polypoidal choroidal vasculopathy were assigned to 1 of the 3 groups. The patients in Group 1 (n = 11) received 1 session of PDT. The patients in Group 2 (n = 10) received 3 monthly intravitreal injections of 0.5 mg ranibizumab, and the patients in Group 3 (n = 9) received 1 session of PDT and 3 injections of 0.5 mg ranibizumab. Retreatment, with the same therapeutic scheme in each group, was considered in case of leaking polyps on the indocyanine green angiography in Groups 1 and 3 and persistence or recurrence of subretinal fluid, intraretinal fluid, and/or hemorrhages in Group 2. Results: All the patients completed 12 months of follow-up. The visual acuity in the patients of Group 1 improved by 0.25 logarithm of the minimum angle of resolution units (P < 0.001), whereas the differences in the visual acuity in the other 2 groups were not statistically significant (0.04 logarithm of the minimum angle of resolution, P = 0.8118 in Group 2 and 0.18 logarithm of the minimum angle of resolution, P > 0.05 in Group 3). Of the patients in Group 1, 45.45% gained more than 3 lines (P = 0.0056), whereas no patient in Groups 2 and 3 experienced such a difference. No patient in Group 1 and 11.1% (n = 1) in Group 3 had angiographically evident polyps at 12 months, whereas 90% (n = 9) of the patients in Group 2 had persistent leakage. No extensive submacular hemorrhage or other complications were noted during the follow-up period. Conclusion: Photodynamic therapy resulted in a significantly better outcome at the end of the follow-up, whereas the patients who received ranibizumab or PDT and ranibizumab experienced a stabilization of the disease.

Intravitreal ranibizumab for the treatment of inflammatory choroidal neovascularization.

Purpose: To evaluate the effect of individualized repeated intravitreal injections of ranibizumab (Lucentis) on visual acuity and central foveal thickness in patients with choroidal neovascular membrane (CNV) associated with various ocular inflammatory clinical entities. Methods: Our study was a retrospective, noncomparative, interventional, and observational case series. Sixteen eyes of 15 consecutive patients diagnosed with inflammatory CNV treated with repeated intravitreal injections of ranibizumab were evaluated. The underlying diagnoses were toxoplasmosis (n = 4), serpiginous choroidopathy (n = 2), punctate inner choroidopathy (n = 5), multifocal choroiditis (MFC, n = 3), and scleroderma (n = 2). All patients underwent monthly optical coherence tomography (OCT) scans and fluorescein angiography/indocyanine green angiography every 1 month after every injection and then every 3 months. Optical coherence tomography scans and fluorescein angiography were performed by the same experienced physician. Repeated intravitreal injections were performed when persistent/recurrent fluid on OCT and/or signs of active CNV on angiography were present. Changes in Early Treatment Diabetic Retinopathy Study visual acuity and central foveal thickness were statistically analyzed. Results: The mean follow-up time was 70.4 ± 24 weeks (17.6 months; range, 44-116 weeks [11-29 months]). The mean number of injections performed was 2.3, and the mean best-corrected visual acuity improved from 55 Early Treatment Diabetic Retinopathy Study letters (logarithm of the minimum angle of resolution, 0.9 ± 0.4 [mean ± SD]) at baseline to 70.3 Early Treatment Diabetic Retinopathy Study letters (logarithm of the minimum angle of resolution, 0.6 ± 0.4) at the end of the follow-up, a statistically significant change compared with baseline (P < 0.0001). The mean letter gain was 15.3 letters, and best-corrected visual acuity improved in 14 of 16 patients (88%) and remained stable in 2 patients (12.5%) without any patient demonstrating deterioration. The mean central foveal thickness (although not excessively increased at baseline) improved from 285 ± 20 μm at baseline to 233 ± 21 μm (statistically significant compared with baseline, P < 0.0001) at the end of the follow-up. At the end of the follow-up, all patients demonstrated CNV regression, and retinal pigment epithelial atrophy surrounding the regressed CNV was developed in 11 of the 16 eyes (68.8%). During the same period, no CNV recurrence was observed and no injection-related complications such as cataract, retinal detachment, endophthalmitis, or exacerbation of uveitis were noted. Conclusion: Overall, our findings suggest that intravitreal injections of ranibizumab have shown promising results in visual acuity improvement and a decrease in macular thickness in patients with inflammatory CNV. Of course, further studies are needed to confirm the exact benefit and standardize the optimal treatment regimen.

Intravitreal ranibizumab (Lucentis) for branch retinal vein occlusion-induced macular edema: nine-month results of a prospective study.

Purpose:The purpose of this study was to evaluate the effect of individualized repeated intravitreal injections of ranibizumab (Lucentis, Genentech, South San Francisco, CA) on visual acuity and central foveal thickness (CFT) for branch retinal vein occlusion-induced macular edema. Methods:This study was a prospective interventional case series. Twenty-eight eyes of 28 consecutive patients diagnosed with branch retinal vein occlusion-related macular edema treated with repeated intravitreal injections of ranibizumab (when CFT was >225 μm) were evaluated. Optical coherence tomography and fluorescein angiography were performed monthly. Results:The mean best-corrected distance visual acuity improved from 62.67 Early Treatment of Diabetic Retinopathy Study letters (logarithm of the minimum angle of resolution = 0.74 ± 0.28 [mean ± standard deviation]) at baseline to 76.8 Early Treatment of Diabetic Retinopathy Study letters (logarithm of the minimum angle of resolution = 0.49 ± 0.3; statistically significant, P < 0.001) at the end of the follow-up (9 months). The mean letter gain (including the patients with stable and worse visual acuities) was 14.3 letters (2.9 lines). During the same period, 22 of the 28 eyes (78.6%) showed improved visual acuity, 4 (14.2%) had stable visual acuity, and 2 (7.14%) had worse visual acuity compared with baseline. The mean CFT improved from 349 ± 112 μm at baseline to 229 ± 44 μm (significant, P < 0.001) at the end of follow-up. A mean of six injections was performed during the follow-up period. Our subgroup analysis indicated that patients with worse visual acuity at presentation (≤50 letters in our series) showed greater visual benefit from treatment. “Rebound” macular edema was observed in 5 patients (17.85%) at the 3-month follow-up visit and in none at the 6- and 9-month follow-ups. In 18 of the 28 patients (53.6%), the CFT was <225 μm at the last follow-up visit, and therefore, further treatment was not instituted. No ocular or systemic side effects were noted. Conclusion:Individualized repeated intravitreal injections of ranibizumab showed promising short-term results in visual acuity improvement and decrease in CFT in patients with macular edema associated with branch retinal vein occlusion. Further studies are needed to prove the long-term effect of ranibizumab treatment on patients with branch retinal vein occlusion.

The effect of subconjunctival ranibizumab on corneal and anterior segment neovascularization: study on an animal model.

Purpose To evaluate the effect of subconjunctival anti—vascular endothelial growth factor (VEGF) ranibizumab on corneal and anterior segment neovascularization. Methods In this experimental study and laboratory investigation, chemical cauterization was utilized to induce corneal neovascularization in 16 rabbits randomly divided in 2 equal groups. Cauterized eyes were either treated with 0.1 mL (1 mg) of subconjunctival ranibizumab or administered a sham injection. A third group of 4 rabbits served as control for side effects after ranibizumab administration. All animals were monitored daily for 14 days and the extent of corneal scarring and neovascularization was measured on days 1, 7, and 14. After enucleation, ocular tissues were separated under a surgical microscope and VEGF levels were measured with ELISA. Statistical analysis was performed to compare the extent of corneal neovascularization and VEGF levels between treated and untreated eyes. Results Subconjunctival ranibizumab inhibited corneal neovascularization significantly both in the first and the second week compared to untreated controls (p = 0.006 and p = 0.001, respectively). The VEGF levels were significantly lower in all anterior segment tissues like the cornea, iris, aqueous humor, and conjunctiva of the treated eyes (p<0.01). The reduction of VEGF levels ranged from 19% to 73% in different ocular tissues. Corneal scarring was not significantly affected by anti-VEGF treatment (p = 0.7). No side effects were noticed. Conclusions Early subconjunctival administration of ranibizumab may successfully inhibit alkali-induced corneal neovascularization in an animal model. Subconjunctival ranibizumab reduces VEGF levels significantly not only in the cornea and the bulbar conjunctiva but also in the aqueous humor and the iris.

Intravitreal ranibizumab versus thermal laser photocoagulation in the treatment of extrafoveal classic choroidal neovascularization secondary to age-related macular degeneration.

Background: To compare the efficacy of thermal laser photocoagulation versus intravitreal ranibizumab for the treatment of extrafoveal classic choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). Methods: We conducted a retrospective study on 24 eyes with extrafoveal classic CNV secondary to AMD, treated either with thermal laser photocoagulation (group 1) or with intravitreal ranibizumab (group 2). Visual acuity, number of injections/sessions and recurrence rate were assessed. Results: The mean follow-up time was 23.6 ± 2.26 and 19.1 ± 9.74 months for group 1 and 2, respectively. Mean best corrected visual acuity (BCVA) of groups 1 and 2 was 0.59 ± 0.32 and 0.46 ± 0.30 logMAR, respectively (p = 0.343). At the end of the follow-up, mean BCVA of group 1 was 0.92 ± 0.35 and of group 2 0.16 ± 0.12 logMAR and differed statistically compared to baseline (p = 0.02 and p = 0.006, respectively). There was a statistically significant difference between the two groups as far as BCVA at the end of the follow-up was concerned (p < 0.0001). The patients in group 1 received on average 1.38 sessions of thermal laser photocoagulation, while patients in group 2 received on average 4 injections of ranibizumab. The recurrence rate in the laser group was 84.6%, while in the ranibizumab group it was 18.2% (p < 0.001). Specifically, the mean time of recurrence in the laser group was 11.5 months, whereas in the ranibizumab group it was 18 months (p = 0.048). Conclusion: Intravitreal ranibizumab showed promising results in BCVA improvement and decrease in macular thickness in patients with extrafoveal classic CNV due to AMD, with a small number of injections. Laser photocoagulation treatment presented worsening in BCVA and high recurrence rate in our study with long-term follow-up.

Twelve months of follow-up after intravitreal injection of ranibizumab for the treatment of idiopathic parafoveal telangiectasia.

Aims To report the anatomic and functional outcomes of intravitreal ranibizumab in idiopathic parafoveal telangiectasia (IPT). Material and methods Four eyes of three patients were included in this interventional case series. One patient (two eyes) had bilateral IPT (type 2) and two patients (two eyes) had unilateral (type 1) IPT. Retreatment was scheduled in case of leakage persistence in combination with visual acuity (VA) deterioration. Fluorescein angiography and optical coherence tomography were performed together with a full ophthalmic examination at baseline, 1, 3, 6, 9, and 12 months after injection. Results One intravitreal injection of ranibizumab was performed in all four eyes. Complete cessation of leakage was documented postintervention in three eyes and partial cessation in one eye, followed by improvement of best corrected VA in one of them. In all eyes, structural changes of the photoreceptor layer were detected in tomography and were responsible for visual loss, which was in most cases, refractory to the applied therapy. Conclusion Use of ranibizumab might be efficient in eliminating leakage activity in the macular region in patients with IPT. Nevertheless, improvement in VA was infrequent. Preexisting early photoreceptor alteration in IPT might render such patients unable to improve VA.

Effect of Macular Ischemia on Intravitreal Ranibizumab Treatment for Diabetic Macular Edema

Purpose: To evaluate the impact of macular ischemia on the functional and anatomical outcome after intravitreal injections of ranibizumab for the treatment of diabetic macular edema (DME). Procedures: Participants were 49 patients with diabetes mellitus, divided into two groups based on the presence of ischemia on fluorescein angiography: (i) nonischemic group (n = 32) and (ii) ischemic group (n = 17). All patients were treated with intravitreal ranibizumab and were followed up for 6 months. The main outcome measures were changes in visual acuity (VA) and central foveal thickness (CFT). Results: There was a statistically significant improvement in VA and CFT between baseline and the end of the follow-up in the nonischemic group, while in the ischemic group there was no significant difference in VA but CFT differed significantly at the 6-month follow-up. Conclusions: Macular ischemia may have a negative impact on functional outcomes 6 months after intravitreal ranibizumab treatment in patients with DME but has no effect on anatomical outcomes.

Eccentric Macular Hole after Pars Plana Vitrectomy for Idiopathic Macular Hole: A Case Report

Introduction: Postoperative eccentric macular hole (MH) formation is an uncommon complication after pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling for epiretinal membrane or MH treatment. Herein, we present a case of eccentric MH formation after PPV with ILM peeling for MH. Case Description: A 72-year-old female patient underwent 23-gauge PPV with ILM peeling for idiopathic MH in her right eye. The visual acuity was 6/24 in the right eye. One week postoperatively the retina was attached and the MH seemed to be closed, while visual acuity was 6/12. One month after PPV, there was a single eccentric retinal hole below the macula, which was detected at the fundoscopy and was confirmed by OCT. The visual acuity was 6/9 and the patient referred no symptoms. No further intervention was attempted, and at the 6-month follow-up the visual acuity and the size of the eccentric MH remained stable. Conclusions: Eccentric MHs can develop after PPV and are usually managed conservatively by observation.

Reply to the Comment by Ilhan et al. on Our Paper Entitled 'Effect of Macular Ischemia on Intravitreal Ranibizumab Treatment for Diabetic Macular Edema'

dividually and based on fluorescein angiogram findings rather than optical coherence tomography measurements [4] . Of note, the recent results of the RESTORE extension study, which also included patients with ischemia, showed that intravitreal ranibizumab is effective as regards visual acuity and central retinal thickness in patients with DME [5] . On the other hand, DME duration may be a potential prognostic factor for the posttreatment visual outcome in patients with DME, in the sense that the longer DME lasts, the more long-lasting damage it can cause to photoreceptors [6] . In our study, macular ischemia was the main factor examined, and we did not include DME duration in the analysis, since this information was not available for some patients. Furthermore, DME duration is difficult to be determined objectively, as patients could have had the symptom for some time without having realized or they may not visit a doctor promptly. In any case, further prospective studies are needed to determine the effect of DME duration, as good as it can be assumed at the time of DME diagnosis, on the prediction of posttreatment visual outcome in patients with DME. Dear Editor We would like to thank Ilhan et al. [1] for their valuable remark. Our results demonstrated that macular ischemia may have a negative impact on functional outcome at the 6-month follow-up after intravitreal ranibizumab treatment in patients with diabetic macular edema (DME), while an anatomical improvement was noticed, as indicated by the decrease in central retinal thickness [2] . This finding is in line with Chung et al. [3] who reported that, after a short-term follow-up, macular ischemia is a negative prognostic factor of visual outcome in patients with DME treated with intravitreal bevacizumab. Both studies suggested that macular ischemia and subsequent chronic hypoxia cause irreversible damage to photoreceptors, resulting in poor visual outcome despite the structural restoration and resolution of DME after the use of anti-vascular endothelial growth factor agents [2, 3] . Therefore, the principal message of our study was not to avoid intravitreal anti-vascular endothelial growth factor agents in patients with ischemic DME, but to use them with caution, taking into account that the final visual outcome may not be promising. In fact, the decision to treat should be made in each patient inReceived: November 12, 2014 Accepted: November 13, 2014 Published online: December 24, 2014