Daniel Ferraz

Therapies for Neovascular Age-Related Macular Degeneration: Current Approaches and Pharmacologic Agents in Development

As one of the leading causes of blindness, age-related macular degeneration (AMD) has remained at the epicenter of clinical research in ophthalmology. During the past decade, focus of researchers has ranged from understanding the role of vascular endothelial growth factor (VEGF) in the angiogenic cascades to developing new therapies for retinal vascular diseases. Anti-VEGF agents such as ranibizumab and aflibercept are becoming increasingly well-established therapies and have replaced earlier approaches such as laser photocoagulation or photodynamic therapy. Many other new therapeutic agents, which are in the early phase clinical trials, have shown promising results. The purpose of this paper is to briefly review the available treatment modalities for neovascular AMD and then focus on promising new therapies that are currently in various stages of development.

Fundus autofluorescence imaging: Fundamentals and clinical relevance

Fundus autofluorescence (FAF), a relatively new imaging modality, focuses on the fluorescent properties of pigments in the retina to generate images that help us view various disease processes from a different perspective. It aids us in the understanding of the pathophysiology of different retinal disorders. Recently, FAF imaging is being used commonly to help us in the diagnosis, prognosis as well as in determining the treatment response of various retinal disorders. It generates an image based on the distribution pattern of a fluorescent pigment called lipofuscin. Knowing the distribution pattern of lipofuscin in the normal retina is key to understanding an FAF image representing a retinal pathology. Like most other imaging modalities, FAF comes with its own limitations, taking steps to overcome these limitations will be of utmost importance in using this imaging modality to its fullest potential.

A randomized controlled trial of panretinal photocoagulation with and without intravitreal ranibizumab in treatment-naive eyes with non-high-risk proliferative diabetic retinopathy.

Purpose: To compare the efficacy of panretinal photocoagulation (PRP) and intravitreal ranibizumab injection with PRP alone in patients with treatment-naive bilateral non–high-risk proliferative diabetic retinopathy. Methods: Sixty eyes of 30 patients were randomized either to the study group (SG) receiving PRP plus 2 ranibizumab injections or to the control group (CG) receiving PRP alone. Mean change in best-corrected visual acuity and in optical coherence tomography were compared at baseline and 1, 3, and 6 months. Results: Best-corrected visual acuity was significantly better at 6 months in the SG; however, there was decrease in best-corrected visual acuity in the CG. Central macula thickness decreased significantly at 6 months in SG when compared with baseline (−47.6 &mgr;m, P < 0.001) and did not reveal significant difference in the CG. In eyes with diabetic macular edema, best-corrected visual acuity increased by 3.6 letters (P = 0.06) in the SG and decreased by 4.4 letters in the CG (P = 0.003). Central macula thickness decreased by 69.3 &mgr;m (P = 0.001) in the SG and decreased by 45.5 &mgr;m (P = 0.11) in the CG. Conclusion: Intravitreal ranibizumab in combination with PRP can be an effective treatment in eyes with non–high-risk proliferative diabetic retinopathy and diabetic macular edema.

Longitudinal spectral domain optical coherence tomography changes in eyes with intraocular lymphoma

BackgroundCases of patients with primary intraocular lymphoma (PIOL) were retrospectively analyzed to describe the longitudinal intra-retinal morphological changes in PIOL as visualized on images obtained by spectral domain optical coherence tomography (SD-OCT).ResultsIn a retrospective case series, Heidelberg Spectralis SD-OCT images obtained in the longitudinal evaluation of patients with biopsy-proven PIOL were analyzed and assessed. The images were graded for the presence of macular edema (ME), pigment epithelial detachment (PED), subretinal fluid (SRF), and hyperreflective signals. SD-OCT scans of five eyes from five patients were assessed. Patients showed signs of inflammation, such as ME and SRF, which were resolved with treatments in some cases. Hyperreflective signals were found in all eyes in the form of nodules or bands across the retina, with the highest frequency of appearance in the ganglion cell layer, inner plexiform layer, photoreceptor layer, and retinal pigment epithelium; such signals increased with the progression of PIOL.ConclusionSD-OCT may be employed to monitor the progression of PIOL. Hyperreflective signals on OCT may correspond with increase in disease activities, along with other findings such as ME, PED, and SRF.

Variation of choroidal thickness and vessel diameter in patients with posterior non-infectious uveitis

BackgroundChoroidal thickness (CTh) and choroidal vessel diameter (VD) in the Haler’s layer were evaluated as markers of inflammatory insult in non-infectious uveitis (NIU). Spectral-domain optical coherence tomography (Spectralis®, Heidelberg Engineering Inc.) scans were acquired from 23 normal subjects (39 eyes – group 1), 7 subjects with high myopia (14 eyes – group 2), and 19 patients with NIU (23 eyes – group 3). In groups 1 and 2, CTh and VD were measured at 3 different points of the same horizontal OCT scan passing through the fovea and a mean calculated. Mean CTh and VD were calculated in 2 other locations, 2 mm superior and inferior from the chosen foveal horizontal scan. In group 3, three measurements of CTh and VD were obtained within 1 mm of a horizontal scan passing through a retinal lesion; mean CTh and VD were then computed. A ratio (R) between the VD and the corresponding CTh was calculated.ResultsGroup 1, 2 and 3 mean age was 29.6, 29.1 and 45.9 years, respectively. Sixteen normal subjects, three myopic subjects and six NIU patients were male.. Group 1 mean CTh did not differ from group 2 (261.6±45.6 vs. 260.2±50.6 µm µm; p>0.05); mean VD was marginally higher in Group 2 (159.8±32.2 vs. 163.2±33.2 µm; p>0.05). Group 3 demonstrated thinner CTh (193.6±54.6 µm) than Groups 1 and 2 (p = 0.02 and <0.001). Group 3 mean VD (123.6±37.4 µm) was also less than that in Groups 1 and 2; the difference was statistically significant only when compared to group 2, p = 0.01. R did not differ across groups (p-values >0.05), indicating that variations in CTh and VD followed the same trend.ConclusionsThe study reports potential quantitative OCT-derived parameters that may be explored in future trials of non-infectious uveitis. Thinning of choroid and decrease of vessel diameter are observed in patients with chronic NIU compared to controls.

Association of retinal vessel calibre and visual outcome in eyes with diabetic macular oedema treated with ranibizumab.

PurposeThe study aims to identify the association between the baseline retinal vascular calibre and visual outcome of patients with diabetic macular oedema (DMO) treated with intravitreal ranibizumab.MethodsThe 1-M field (as defined in the ETDRS study) of the digital colour fundus photographs of DMO patients who had been treated primarily with ranibizumab in a clinical trial was assessed. Of the 84 patients, 25 had gradable retinal photographs that could be subjected to analyses by the Interactive Vessel Analysis (IVAN) software at baseline. The average retinal vascular calibre of the six largest venules (CRVE) and the six largest arterioles (CRAE) in the peripapillary area (0.5 and 1 disc diameter from the optic disc margin) was measured. The relationship between CRVE and CRAE at baseline and the change in visual acuity at month 12 was assessed using the Mann–Whitney U test.ResultsTen eyes from 10 patients who had shown an improvement of ≥2 lines of best corrected visual acuity (BCVA) at month 12 had a wider baseline CRVE (248.3±24.5 μm) compared with the 15 eyes from 15 patients who did not show the improvement of ≥2 lines (226.6±44.8 μm, P<0.05). The baseline CRAE did not differ significantly in these patients (156.1±22.7 vs 142±17.5 μm, P=0.17).ConclusionsA wider baseline retinal venular calibre may be a predictor of better visual outcome in DMO eyes treated with ranibizumab. Further prospective studies with a larger sample size and a broader range of disease severity and visual acuity are needed to confirm this finding.

Three-monthly intravitreal bevacizumab injections for neovascular age-related macular degeneration: short-term visual acuity results.

Purpose. To evaluate the change in vision after 3 monthly consecutive intravitreal injections of 1.25 mg of bevacizumab for neovascular age-related macular degeneration (AMD). Methods. A retrospective analysis of 35 eyes was performed. Visual acuity (VA) at initial visit and at each follow-up visit was compared. The injection of bevacizumab was performed at 30-day intervals and patients were observed for 5 months after the last injection. Results. Of the 35 eyes, 9 had received previous treatment with photodynamic therapy with or without 4 mg of intravitreal triamcinolone. VA was measured in Snellen table and transformed into logMAR for statistical purposes. Mean age was 76.66 years (range, 49–90 years). There were 24 (69%) women and 11 (31%) men. Mean VA at the initial visit was 0.92±0.50. At month 1, mean VA was 0.84±0.51 and at month 2 was 0.74±0.51. At month 3, mean VA remained 0.74±0.49. Six and 8 months after the initial visit, VA was 0.79±0.49 and 0.77±0.50, respectively. The improvement in VA was statistically significant at month 2 and at the end of the follow-up (8 months) compared with the baseline VA. Conclusions. Three consecutive monthly injections of intravitreal bevacizumab to treat neovascular AMD is effective in improving VA in the short term. Longer prospective studies should be performed to confirm VA stability after the third injection.

Injeção intravítrea de bevacizumab e gás C3F8 para tratamento da hemorragia submacular secundária a degeneração macular relacionada à idade: relato de casos

The purpose of this case series is to describe if the intravitreal use of bevacizumab and perfluoropropane gas (C3F8) would be beneficial to the displacement of subretinal hemorrhage in patients with age-related macular degeneration (AMD). A retrospective study of 5 eyes that received concurrent intravitreal injection of bevacizumab and C3F8 was performed. The results were graded according to blood displacement under the fovea, best final visual acuity and intraoperative complications. At the initial presentation, mean age of patients was 72.6 ± 8.9 years-old and duration of symptoms was 13 ± 9.7 days. From the 5 patients, 3 (60%) were male and 2 (40%) female. The success of submacular hemorrhage full displacement was achieved in 4 patients. The mean preoperative visual acuity (VA) was 1.12 ± 0.34 logMAR and the mean postoperative VA was 0.92 ± 0.4 logMAR. No cases of retinal detachment, endophthalmitis, vitreous hemorrhage, uveitis, cataracts and increased intraocular pressure were noted during the follow-up period. Intravitreal bevacizumab and C3F8 injection, associated to prone position can be a valuable therapeutic option for eyes with neovascular age-related macular degeneration and subretinal hemorrhage to the blood displacement out of the foveal area.

Tomografia de coerência óptica na commotio retinae: relato de caso

The purpose of this case report was to correlate optical coherence tomography findings and visual outcomes of patients with different degrees of commotio retinae. A 20-year-old male and a 23-year-old male that presented with decreased vision due to Berlins edema after blunt ocular trauma were evaluated by optical coherence tomography and retinography. The visual acuity in the affected eye was 20/25 in the first patient and counting fingers in the second one. The ophthalmic examination showed traumatic uveitis and fundoscopy revealed mild retinal opacification in the first case and severe opacification in the latter. The optical coherence tomography confirmed the reduction of foveal depression on the first case and the disarrangement of all retinal layers on the second. There has been complete functional and anatomical resolution by optical coherence tomography in the first patient, while the second evolved to permanent visual loss. Optical coherence tomography is a useful method in the evaluation of retinal trauma, helping to understand its physiopathology and to predict its prognosis through the anatomical analysis of the affected region.

Idiopathic polypoidal choroidal vasculopathy masquerading as choroidal tumors: one year follow-up of a peripheral lesion

This case report describes peripheral idiopathic polypoidal choroidal vasculopathy (IPCV) with a collection of small aneurysmal dilations that masqueraded as choroidal tumors in an elderly patient. A 68-year-old African American woman was referred to us with a suspected diagnosis of asymptomatic vascular choroidal tumor and choroidal capillary hemangioma, affecting the temporal peripheral fundus. Upon examination, optical coherence tomography (OCT) revealed two large hemorrhagic pigment epithelium detachments (PED), and indocyanine green angiography (ICG) confirmed the diagnosis of IPCV. One year later, there was reduction in the hemorrhagic pigment epithelium detachments and the lesion took on a different appearance, resembling a choroidal osteoma. No treatment was necessary despite the presence of multiple polyps. IPCV is a rare condition that can resemble other choroidal diseases depending on the stage of presentation. OCT is the best tool to determine the characteristics of the lesions, and indocyanine green angiography should be used to confirm the diagnosis. Not all cases require treatment.