Eleonora Corbelli

Optical Coherence Tomography Angiography of Diabetic Retinopathy

PURPOSE To describe the optical coherence tomography angiography (OCTA) features of diabetic retinopathy. METHODS Literature review and case series. RESULTS Four cases are presented. CONCLUSION OCTA is an effective method for evaluating retinal changes in diabetic retinopathy and represents a novel complement or alternative to fluorescein angiography. Although OCTA should currently be considered an investigational technique, in the near future, it may play key roles in the diagnosis and management of diabetic retinopathy.

Recent advances in the management of dry age-related macular degeneration: A review

Age-related macular degeneration (AMD), the most important cause of vision loss in elderly people, is a degenerative disorder of the central retina with a multifactorial etiopathology. AMD is classified in dry AMD (d-AMD) or neovascular AMD depending on the presence of choroidal neovascularization. Currently, no therapy is approved for geographic atrophy, the late form of d-AMD, because no treatment can restore the damage of retinal pigment epithelium (RPE) or photoreceptors. For this reason, all treatment approaches in d-AMD are only likely to prevent and slow down the progression of existing atrophy. This review focuses on the management of d-AMD and especially on current data about potential targets for therapies evaluated in clinical trials. Numerous examinations are available in clinics to monitor morphological changes in the retina, RPE and choroid of d-AMD patients. Fundus autofluorescence and optical coherence tomography (OCT) are considered the most useful tools in the diagnosis and follow-up of d-AMD alterations, including the monitoring of atrophy area progression. Instead, OCT-angiography is a novel imaging tool that may add further information in patients affected by d-AMD. Several pathways, including oxidative stress, deposits of lipofuscin, chronic inflammation and choroidal blood flow insufficiency, seem to play an important role in the pathogenesis of d-AMD and represent possible targets for new therapies. A great number of treatments for d-AMD are under investigation with promising results in preliminary studies. However, only few of these drugs will enter the market, offering a therapeutic chance to patients affected by the dry form of AMD and help them to preserve a good visual acuity. Further studies with a long-term follow-up would be important to test the real safety and efficacy of drugs under investigation.

Optical coherence tomography angiography in the evaluation of geographic atrophy area extension

Purpose To investigate the application of optical coherence tomography angiography (OCT-A) in evaluation of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Methods Patients with GA were prospectively enrolled and studied with blue fundus autofluorescence (FAF), en face structural OCT, and OCT-A. OCT-A images were acquired using a slab of whole choroid, whereas en face structural OCT images were obtained at the ellipsoid zone (EZ), at the choroidal (CH) level, and at the scleral (SC) level. Three readers independently measured the GA extension areas and evaluated the foveal sparing in each examination. Intraobserver/interobserver agreements and agreement between each couple of imaging techniques were assessed. Results A total of 47 eyes (26 patients, mean age 76 ± 7 years) with GA (mean area using FAF: 8.77 ± 5.00 mm2) were included. Intraobserver and interobserver agreement was excellent for all imaging techniques (intraclass correlation coefficient [ICC] > 0.985), even if en face EZ structural OCT revealed the poorest quality agreement limits. Considering the analysis between each couple of imaging techniques, ICC was excellent between OCT-A compared with FAF (ICC: 0.995), followed by en face structural OCT at CH level (ICC: 0.992), at SC level (ICC: 0.986), and at EZ level (ICC: 0.973). No differences were detected between multifocal and monofocal GA lesions. Considering the evaluation of foveal involvement, lower agreements were disclosed between FAF and all other imaging techniques. Conclusions OCT-A is a reliable technique for easily visualizing and quantifying GA with the advantages, compared to current imaging techniques, of offering together both structural and blood flow information regarding retinal and choroidal layers and excluding choroidal neovascularization.

Choroidal Round Hyporeflectivities in Geographic Atrophy.

Purpose In geographic atrophy (GA), choroidal vessels typically appear on structural optical coherence tomography (OCT) as hyperreflective round areas with highly reflective borders. We observed that some GA eyes show choroidal round hyporeflectivities with highly reflective borders beneath the atrophy, and futher investigated the charcteristcs by comparing structural OCT, indocyanine green angiography (ICGA) and OCT angiography (OCT-A). Methods Round hyporeflectivities were individuated from a pool of patients with GA secondary to non-neovascular age-related macular degeneration consecutively presenting between October 2015 and March 2016 at the Medical Retina & Imaging Unit of the University Vita-Salute San Raffaele. Patients underwent a complete ophthalmologic examination including ICGA, structural OCT and OCT-A. The correspondence between choroidal round hyporeflectivities beneath GA on structural OCT and ICGA and OCT-A imaging were analyzed. Results Fifty eyes of 26 consecutive patients (17 females and 9 males; mean age 76.8±6.2 years) with GA were included. Twenty-nine round hyporeflectivities have been found by OCT in choroidal layers in 21 eyes of 21 patients (42.0%; estimated prevalence of 57.7%). All 29 round hyporeflectivities showed constantly a hyperreflective border and a backscattering on structural OCT, and appeared as hypofluorescent in late phase ICGA and as dark foci with non detectable flow in the choroidal segmentation of OCT-A. Interestingly, the GA area was greater in eyes with compared to eyes without round hyporeflectivities (9.30±5.74 and 5.57±4.48mm2, respectively; p = 0.01). Conclusions Our results suggest that most round hyporeflectivities beneath GA may represent non-perfused or hypo-perfused choroidal vessels with non-detectable flow.

Nine-Year Outcome of Ranibizumab Monotherapy for Choroidal Neovascularization Secondary to Pathologic Myopia

Purpose: The aim of this study was to evaluate the 9-year outcome of ranibizumab monotherapy for myopic choroidal neovascularization (mCNV). Methods: This was a retrospective, nonrandomized, multicentric study to evaluate the long-term outcomes of mCNV treated with ranibizumab monotherapy for at least 9 years according to a strict pro re nata regimen. Results: Seventeen eyes of 17 patients (12 women, mean age 57.9 ± 7.7 years) were included. The mean follow-up period was 112.4 ± 3.9 months (range 108–120). The mean difference in best-corrected visual acuity (BCVA) from baseline to the last follow-up was +1.2 ± 15.6 ETDRS letters (p = 0.004, between initial vs. 12 and 24 months). The mean total number of intravitreal injections for each patient was 1.24 ± 1.70 per year (range 2–25). No systemic adverse reactions related to the drug treatment were detected during the 9-year follow-up period. Conclusions: Long-term ranibizumab monotherapy treatment induces unchanged or better BCVA compared to baseline after a 9-year treatment in almost all eyes.

Optical coherence tomography angiography in pseudophakic cystoid macular oedema compared to diabetic macular oedema: qualitative and quantitative evaluation of retinal vasculature

Aims To describe optical coherence tomography angiography (OCT-A) abnormalities of patients with pseudophakic cystoid macular oedema (PCMO) before and after pharmacological resolution, compared with diabetic macular oedema (DMO) and normal eyes. Methods In this retrospective, observational study, 44 eyes (30 patients) were included: 15 eyes (15 patients) affected by PCMO; 14 healthy fellow eyes used as negative control group; 15 eyes (15 age-matched and sex-matched patients) with DMO used as positive control group. All patients underwent a complete ophthalmological examination at baseline, including OCT-A scans of the macula through AngioPlex CIRRUS-5000 (Carl Zeiss Meditec, Dublin, USA). Patients with PCMO and DMO were re-evaluated after the pharmacological resolution of cystoid macular oedema (CMO). Results Disruption of parafoveal capillary arcade and cystoid spaces in deep capillary plexus (DCP) were frequent in patients with PCMO and DMO (73% and 100%, 87% and 100%). Capillary abnormalities and non-perfusion greyish areas in DCP were more frequent in DMO (P<0.001 and P=0.014). Patients with PCMO showed a larger foveal avascular zone area in DCP at baseline (P<0.001), which significantly reduced after treatment (P=0.001). Vessel density of full-thickness retina and DCP was reduced in patients with PCMO (P=0.022 and P=0.001), and no changes were observed after treatment. Interestingly, DCP appeared less represented in patients with DMO than PCMO subjects (P=0.001). Conclusions Patients with PCMO have an impairment of mainly DCP, partially reversible after treatment. Furthermore, we disclosed that different alterations of the retinal vasculature characterise CMO derived from two different diseases, namely PCMO and DMO, and this could be due to their distinct pathophysiology.

Multimodal Imaging of Diabetic Retinopathy in a Patient With Fovea Plana.

A 41-year-old man presented to our department with diagnosis of Type 1 diabetes and diabetic retinopathy. Best-corrected visual acuity was 20/20 in both eyes, and on slit-lamp biomicrospcopy, anterior segments were unremarkable. Ultra-widefield (California; Optos plc, Dunfermline, Scotland) fluorescein angiography showed inactive proliferative diabetic retinopathy because of panretinal photocoagulation in both eyes. Central assessment by fluorescein angiography revealed the absence of foveal avascular zone along Fig. 1. Fluorescein angiography reveals the absence of foveal avascular zone along with occurrence of microaneurysms in the central fovea (A and B). Spectral domain optical coherence tomography B-scans centered on the fovea show persistence of inner retinal layers (A and B) and reveal a microaneurysm beneath the outer plexiform layer (A). Optical coherence tomography angiography (OCTA) shows preservation of both superficial and deep capillary plexuses despite foveal avascular zone (C and D), and better visualization of a microaneurysm in the deep capillary plexus (C, arrowhead). Optical coherence tomography angiography in a normal eye showing for comparison the absence of both superficial and deep capillary plexuses in the central fovea (i.e., foveal avascular zone) (E).

Optical Coherence Tomography Angiography Demonstration of Choroidal Neovascularization in Malattia Leventinese.

In a case of Malattia Leventinese, optical coherence tomography angiography led to the diagnosis of type 1 neovascularization, despite absence of evidence on conventional dye-based angiography. The authors hypothesize that, at least in some cases, accumulation of subretinal fluid in Malattia Leventinese could be due to a subretinal pigment epithelium (RPE) neovascular component rather than creation of hydrophobic barrier at the RPE and Bruchs membrane. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:602-604.].

Neun-Jahres-Ergebnisse zur Ranibizumab-Monotherapie der choroidalen Neovaskularisation infolge pathologischer Myopie

Zweck: Mit der vorliegenden Studie sollten die 9-Jahres-Ergebnisse der Behandlung der myopen choroidalen Neovaskularisation (mCNV) mit Ranibizumab als Monotherapie beurteilt werden. Methoden: Es handelt sich um eine retrospektive, nicht randomisierte Multicenterstudie zur Beurteilung der Langzeitergebnisse einer mindestens 9-jährigen Behandlung der mCNV mit Ranibizumab als Monotherapie gemäß einem streng bedarfsbasierten Therapieschema. Ergebnisse: In die Studie wurden 17 Augen von 17 Patienten (12 Frauen; Durchschnittsalter 57,9 ± 7,7 Jahre) eingeschlossen. Die mittlere Nachbeobachtungsdauer betrug 112,4 ± 3,9 Monate (Spanne: 108-120). Die mittlere Differenz in der bestkorrigierten Sehschärfe (BCVA) zwischen dem Ausgangswert und der letzten Nachuntersuchung lag bei +1,2 ± 15,6 ETDRS (Early Treatment for Diabetic Retinopathy Study)-Buchstaben (p = 0,004, Ausgangswert vs. 12 und 24 Monate). Die mittlere Gesamtzahl intravitrealer Injektionen bei jedem Patienten betrug 1,24 ± 1,70 pro Jahr (Spanne: 2-25). Während der 9-jährigen Nachbeobachtung wurden keine systemischen Nebenwirkungen im Zusammenhang mit der Arzneimitteltherapie beobachtet. Schlussfolgerungen: Die Langzeit-Monotherapie mit Ranibizumab bewirkt nach 9-jähriger Behandlung bei fast allen Augen eine gegenüber Studienbeginn unveränderte oder verbesserte BCVA. Übersetzung aus Ophthalmologica 2018;239:133-142 (DOI: 10.1159/000485112)

Diagnosis, management and future treatment options for adult-onset foveomacular vitelliform dystrophy

ABSTRACT Introduction: Adult-onset foveomacular vitelliform dystrophy is a prevalent form of macular degeneration and typically occurs between the fourth and sixth decades of life. Areas covered: A pubmed and medline search was performed using the relevant key words. Several variants of the term ‘adult-onset vitelliform macular dystrophy’ were searched in relation to different terms: ‘diagnosis’, ‘managment’ and ‘treatment’. Expert commentary: Multimodal diagnostic imaging methods such as autofluorescence, fluorescein angiography, indocyanine green angiography, structural spectral domain optical coherence tomography, and optical coherence tomography angiography have led to a better understanding of the pathophysiological features of macular diseases. Gene therapy is a promising future option for treating monogenic forms of adult-onset foveomacular vitelliform dystrophy.