Ilaria Zucchiatti

Pathophysiology and treatment of diabetic retinopathy.

In the past years, the management of diabetic retinopathy (DR) relied primarily on a good systemic control of diabetes mellitus, and as soon as the severity of the vascular lesions required further treatment, laser photocoagulation or vitreoretinal surgery was done to the patient. Currently, even if the intensive metabolic control is still mandatory, a variety of different clinical strategies could be offered to the patient. The recent advances in understanding the complex pathophysiology of DR allowed the physician to identify many cell types involved in the pathogenesis of DR and thus to develop new treatment approaches. Vasoactive and proinflammatory molecules, such as vascular endothelial growth factor (VEGF), play a key role in this multifactorial disease. Current properly designed trials, evaluating agents targeting VEGF or other mediators, showed benefits in the management of DR, especially when metabolic control is lacking. Other agents, directing to the processes of vasopermeability and angiogenesis, are under investigations, giving more hope in the future management of this still sight-threatening disease.

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.

Choroid Thickness Measurement with RTVue Optical Coherence Tomography in Emmetropic Eyes, Mildly Myopic Eyes, and Highly Myopic Eyes:

Purpose. To evaluate choroid thickness (CT) with RTVue spectral domain optical coherence tomography (SD-OCT) and the effect of age and myopia in eyes without posterior complications. Methods. In this multicenter cross-sectional study, all enrolled patients were over age 18 and divided them in 3 groups based on refraction: emmetropia (+1 D to −1 D), mild myopia (–1 D to −6 D), and high myopia (–6 D to −20 D) groups. Horizontal scans through the fovea were acquired with RTVue OCT (Optovue Inc., Fremont, California, USA). Choroid thickness was measured at 500 µm intervals up to 1,500 µm temporal and nasal to the fovea by 2 graders. Mean CT was calculated based on the average of the 7 locations. Statistical analysis was performed to evaluate CT at each location, the effects of age and myopia, and grader agreement. Results. A total 85 eyes of 85 subjects (30 emmetropic, 24 myopic, and 31 high myopic) were enrolled. Excellent grader agreement was observed with an intraclass correlation coefficient (ICC) >0.97. The mean CT was 248.2±78.5 (µm) for emmetropia (age = 58±18), 247.0±85.4 (µm) for myopia (age = 45±20), and 131.5±70.9 (µm) for high myopia (age = 54±13). The mean CT was not significantly different between emmetropia and myopia groups, which were significantly thicker than high myopia group. The overall slope of age-related change for the mean CT was −1.95 µm/y and the effect of age differed among the groups. Conclusions. Choroid thickness can be measured from RTVue OCT images with good reproducibility. Age and high myopia appear to negatively affect CT. The age effect may vary with refraction groups.

SD-OCT pattern of retinal venous occlusion with cystoid macular edema treated with Ozurdex®.

Purpose To report our experience with sustained-release dexamethasone 0.7 mg intravitreal implant (Ozurdex®; Allergan, Inc., Irvine, CA) in retinal vein occlusion with macular edema. Methods A prospective study of a series of 9 patients with recent retinal vein occlusion with macular edema treated with sustained-release dexamethasone 0.7 mg intravitreal implant was performed. Complete ophthalmic examination including visual acuity, fundus biomicroscopy, fundus photography, fluorescein angiography, and spectral domain optical coherence tomography (Spectralis SD-OCT; Heidelberg Engineering, Heidelberg, Germany) was performed at baseline and follow-up (1 week, 1 month, and 3 months), and tolerability of the implant was assessed. Results Nine eyes of 9 consecutive patients treated with a total of 9 sustained-release dexamethasone 0.7 mg intravitreal implants for macular edema associated with retinal vein occlusion were included. Five patients had central retinal vein occlusion and 4 patients had branch retinal vein occlusion. Accentuated ischemia was associated in 2/5 patients with central retinal vein occlusion. All eyes showed SD-OCT evidence of decreased edema following implant placement (mean decrease in central retinal thickness 320 μm). All eyes showed decrease of serous detachment of the neurosensory retina (not present in 7/9 cases at 1 month). Intraretinal central cyst resolved in 7/9 cases; small peripheral cysts were persistent in only 2/9 cases. Spectral domain optical coherence tomography demonstrated the presence and the integrity of external limiting membrane and inner and outer segments (IS/OS) of the photoreceptors in 6/9 cases at month 3. Forty percent of patients gained ≥10 letters of best-corrected visual acuity at 3 months. The safety profile was consistent with the results of a previous phase III trial of Ozurdex®, and no serious ocular or systemic adverse events were observed during the follow-up period. Conclusions In patients with macular edema in retinal vein occlusion, sustained-release dexamethasone 0.7 mg intravitreal implant may be an effective treatment option to control macular edema. At the final visit, foveal thickness was decreased to physiologic levels in all eyes. In parallel with resolution of the macular edema, visual acuity was significantly improved at the final visit. However, final visual acuity in eyes with still interrupted or thickened IS/OS interface was significantly poorer than that in eyes with a normal IS/OS line.

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.

Compassionate use of dexamethasone implant for the treatment of macular edema secondary to central retinal vein occlusion in a clinical setting

to be involved in photoreceptor degeneration in retinal detachment (Nakazawa et al. 2011). Improved visual function and absence of malaise during repeated anti-thymocyte therapy are compatible with only the first infusion of anti-thymocyte globulin resulting in significant cytokine release (Guttmann et al. 1997). In conclusion, our observation suggests that cytokines released from T cells that disintegrated as a result of anti-thymocyte globulin infusion may have been be involved in the development of AMN.

Intravitreal Bevacizumab for Subfoveal Choroidal Neovascularization Associated with Pattern Dystrophy

PURPOSE To assess the effects of intravitreal bevacizumab injections in the treatment of subfoveal choroidal neovascularization (CNV) associated with pattern dystrophy (PD) of the retinal pigment epithelium. METHODS The study was a prospective, nonrandomized, open-label, interventional clinical trial in which 12 patients were prospectively enrolled. Patients with a diagnosis of PD complicated by subfoveal CNV were considered for the study. All patients underwent a complete ophthalmic examination, including ETDRS visual acuity measurement, electroretinogram, electrooculogram, optical coherence tomography, and fluorescein angiography. The treatment protocol began with a loading dose of three consecutive injections at 1-month intervals, followed by injections administered as needed, according to OCT parameters and angiographic features observed during a 24-month follow-up period. The number of eyes with a visual acuity loss of fewer than 15 letters (<3 ETDRS lines), compared with baseline measures, was recorded at the 6-, 12-, and 24-month examinations. RESULTS Twelve patients completed the planned visits and were included in the study. A visual acuity loss of fewer than 15 letters was not registered in any case at the 6- and 12-month examinations and was found in only one (8%) patient at the 24-month examination. The mean best corrected visual acuity (BCVA) and the mean central macular thickness (CMT) at baseline were 0.73+/-0.34 (logMAR+/-SD) and 276+/-95 microm (SD), respectively. At the 3-month examination, the mean BCVA significantly improved to 0.48+/-0.27, whereas the mean CMT decreased to 220+/-71 microm. At the 12-month examination, the mean BCVA was 0.45+/-0.24, and the mean CMT was 209+/-53 microm. At the 24-month (last) follow-up, the BCVA showed substantial stabilization and the CMT decreased to 199+/-34 microm. No side effects or complications were registered. CONCLUSIONS Intravitreal bevacizumab injection is a beneficial treatment for subfoveal CNV associated with PD. Further studies are warranted to confirm these initial results and to analyze the morphofunctional changes during the follow-up. (ClinicalTrials.gov number, NCT00391144.).

Optical coherence tomography angiography of myopic choroidal neovascularisation

Background/aims To describe the morphological features of choroidal neovascularisation (CNV) and to report the ability of optical coherence tomography angiography (OCT-A) to detect the presence of myopic CNV by means of this new technique. Methods Myopic CNV cases were individuated from a pool of patients with pathological myopia consecutively presenting between October 2015 and March 2016. OCT-A images were assessed for classification of morphological features, and to estimate sensitivity and specificity. Results Thirty-six eyes of 28 consecutive patients with myopic CNV were included. In 4 out of 36 eyes it was not possible to classify the CNV ‘shape’, ‘core’, ‘margin’ and ‘appearance’ because the vascular network was not clearly visualised due to the poor quality of the examination. CNV shape on OCT-A was rated as circular in 9 eyes and irregular in 23 eyes. CNV core was visible in 11 eyes. CNV margin was considered as well defined in 16 eyes and poorly defined in 16 eyes. CNV appearance showed an ‘interlacing’ aspect in 16 eyes and a ‘tangled’ aspect in the other 16 eyes. A total of 11 CNVs were defined as active, 9 of which (81.8%) were interlacing, while a total of 21 were inactive, 14 of which (66.7%) were tangled. OCT-A sensitivity turned out to be 90.48% and specificity was 93.75%. Conclusions We describe the OCT-A features of myopic CNV secondary to pathological myopia and demonstrate its high sensitivity and specificity for neovascular detection. Qualitative evaluation of OCT-A characteristics may allow one to recognise different patterns, possibly corresponding to different degrees of neovascular activity.

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.

CLINICAL SPECTRUM OF MACULAR-FOVEAL CAPILLARIES EVALUATED WITH OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

Purpose: To describe macular-foveal capillaries (MFC) by means of optical coherence tomography angiography and to identify the clinical spectrum of this angiographic feature. Methods: Patients with MFC presenting at the Medical Retina & Imaging Unit of the Department of Ophthalmology, University Vita-Salute San Raffaele in Milan were recruited. Patients underwent a complete ophthalmologic examination that included slit-lamp examination, fundus examination, measurement of best-corrected visual acuity, fundus autofluorescence, and spectral-domain optical coherence tomography (Spectralis HRA + OCT; Heidelberg Engineering, Heidelberg, Germany). Fluorescein angiography was performed in selected cases. Optical coherence tomography angiography was performed through Zeiss prototype (AngioPlex, CIRRUS HD-OCT models 5000; Carl Zeiss Meditec, Inc, Dublin, OH). Results: Twelve eyes of 10 consecutive white patients (5 men and 5 women; 50%) presenting MFC were included. Mean age was 66.2 ± 10.2 years (range, 53–79 years); mean best-corrected visual acuity was 0.1 ± 0.13 logarithm of the minimum angle of resolution (range, 0–0.4 logarithm of the minimum angle of resolution, corresponding to 20/20 to 20/50). Mean central macular thickness was 348 ± 57.6 &mgr;m. Two patients were affected by macular pucker, two by postsurgical macular edema, two by age-related macular degeneration, one by diabetic retinopathy, one by dome-shaped macula, one presented with chronic serous chorioretinopathy, and one with branch artery occlusion. Six eyes disclosed a complete absence of the foveal avascular zone, whereas the six other cases showed a partial foveal avascularity. No significant difference was found between complete and incomplete MFC with regards to best-corrected visual acuity (P = 0.272) and central macular thickness (P = 0.870). Conclusion: Cases of persistent MFC are heterogeneous in demographic characteristics, fundus appearance, and visual function. However, MFC, presenting either as complete absence of the foveal avascular zone or only partial foveal avascularity, may complicate different retinal abnormalities or represents a coincident finding.