Carlo La Spina

Repeated intravitreal dexamethasone implant (Ozurdex) for diabetic macular edema.

Purpose: To evaluate the effects of repeated intravitreal dexamethasone implant. Methods: We reviewed the charts of 12 patients with diabetic macular edema, who received at least 2 intravitreal Ozurdex (0.7 mg) on an “as needed” basis. Main outcome measures included changes in best-corrected visual acuity, central macular thickness, retreatment interval, and incidence of side effects. Results: A total of 15 eyes of 12 patients (6 men, 6 women; mean age 62 ± 12 years) were included. Retreatment was judged necessary after mean of 7.8 ± 4.1 months from the first Ozurdex (median, 6 months) (15 of 15 eyes), mean of 4.8 ± 0.9 months from the second Ozurdex (median, 5 months) (7 of 15 eyes), mean of 5.3 ± 1.5 months from the third Ozurdex (median, 5 months) (3 of 15 eyes), and mean of 5.6 ± 2 months from the fourth Ozurdex (median, 5 months) (3 of 15 eyes). Mean baseline best-corrected visual acuity was 0.67 ± 0.33 logMAR in the overall diabetic macular edema population; it significantly improved to 0.53 ± 0.31 logMAR after mean of 40.9 ± 18.2 days from the first Ozurdex (peaking efficacy) (P < 0.001), to 0.53 ± 0.29 logMAR after mean of 34.4 ± 9.0 days from the second Ozurdex (peaking efficacy) (P < 0.003), and stabilized to 0.62 ± 0.26 logMAR after mean of 29.8 ± 12.1 days from the third Ozurdex (peaking efficacy) (P = 0.05), to 0.5 ± 0.26 logMAR after mean of 36.3 ± 3.2 days from the fourth Ozurdex (peaking efficacy) (P = 0.2), and to 0.50 ± 0.26 logMAR after mean of 37.0 ± 2.6 days from the fifth Ozurdex (peaking efficacy) (P = 0.2). Mean baseline central macular thickness significantly decreased from 546 ± 139 &mgr;m to 292 ± 43 &mgr;m at 39.4 ± 17.9 days from the first Ozurdex (peaking efficacy) (P < 0.001), to 297 ± 47 &mgr;m at 33 ± 9.4 days from the second Ozurdex (peaking efficacy) (P < 0.001), to 293 ± 22 &mgr;m at 29.8 ± 12.1 days from the third Ozurdex (peaking efficacy) (P = 0.01), and stabilized to 309 ± 35 &mgr;m at 36.3 ± 3.2 days from the fourth Ozurdex (peaking efficacy) (P = 0.1), and to 295 ± 7 &mgr;m at 37.0 ± 2.6 days from the fifth Ozurdex (peaking efficacy) (P = 0.1). No serious adverse events were observed; three eyes developed a transient intraocular pressure increase, and cataract was extracted in one eye. Conclusion: Repeated intravitreal Ozurdex on an “as needed” basis with a variable retreatment interval may produce long-term clinically meaningful benefits in the treatment of diabetic macular edema, without other significant side effects than expected after intraocular corticosteroid treatment.

Intravitreal ranibizumab for choroidal neovascularization with large submacular hemorrhage in age-related macular degeneration.

Purpose: To evaluate the effects of intravitreal ranibizumab injections in the treatment of choroidal neovascularization with large submacular hemorrhage secondary to age-related macular degeneration. Methods: Prospective interventional case series. Patients presenting occult choroidal neovascularization with flat large submacular hemorrhage >50% of the entire lesion were considered. The protocol required 3 monthly consecutive injections, followed by repeat injections over the 12-month follow-up on the basis of optical coherence tomography parameters and angiographic features. Results: Twenty-three patients were enrolled in the study and prospectively followed up. Mean best-corrected visual acuity and mean central macular thickness at the baseline were 0.82 ± 0.22 (logarithm of the minimum angle of resolution ± standard deviation) and 342 ± 56 µm, respectively. At 12-month examination, mean visual acuity improved significantly to 0.68 ± 0.41 (P = 0.04), and mean central macular thickness decreased to 236 ± 26 µm (P < 0.0001). A progressive resolution of macular bleeding was registered in 22 of 23 patients. No side effect or complication was registered. Conclusion: Intravitreal ranibizumab can be considered a beneficial approach for the management of choroidal neovascularization with flat large submacular hemorrhage secondary to age-related macular degeneration.

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.

Reproducibility and reliability of optical coherence tomography angiography for foveal avascular zone evaluation and measurement in different settings

Purpose: Optical coherence tomography angiography (OCTA) allows delineating the foveal avascular zone (FAZ) easily and noninvasively. The present study aims to test reproducibility and reliability of FAZ evaluation by means of OCTA in different settings. Methods: Twenty-four eyes of 24 normal subjects were investigated using AngioVue OCTA Imaging System. A series of OCTA acquisitions were taken both in basal and in different experimental settings after vasoactive stimuli. Images were evaluated separately by two operators and FAZ area was measured both manually and using the built-in automated measurement tool. Results: No differences for FAZ area were found in the repetition of basal acquisitions, neither in manual nor in automated measurement (0.215 ± 0.06 vs. 0.216 ± 0.07, and 0.268 ± 0.05 vs. 0.264 ± 0.09, first vs. second basal measurement in square millimetres for manual and automated evaluation, P = 0.25 and P = 0.35, respectively). Interoperators correlation was optimal (r2 = 0.978 [95% CI 0.981–0.976]). No differences were found among the other settings, which included first basal and then repeated (second) in the morning, after flickering light stimulus, after a Bruce treadmill stress test, after 30 minutes dark adaptation, and basal in the evening, neither in automated nor in manual measurements. Automated measurements for nonflow areas provided significantly larger diameters than manual ones. Conclusion: AngioVue OCTA Imaging System produces highly reproducible FAZ images with a high interoperators concordance level. Optical coherence tomography angiography capability to detect FAZ area seems not to be influenced by any of the vasoactive stimuli considered in the current study. Nonflow areas seem to be larger when measured automatically than manually.

Clinical features of patients with episcleritis and scleritis in an Italian tertiary care referral center.

Purpose To evaluate demographic characteristics, clinical features, systemic disease associations, visual outcomes, and treatment modalities of patients with episcleritis and scleritis in an Italian tertiary care referral center. Methods Data from 25 patients with episcleritis and from 85 patients with scleritis followed from 2003 to 2012 were retrospectively evaluated. The main outcome measures were demographics, ocular disease characteristics, presence of systemic associated disease, treatment regimen, and follow-up period. Results Episcleritis and scleritis were found bilaterally in 24% and 31% of patients, respectively (p<0.521). The episcleritis was diffuse in 15 and focal in 10 patients, while the scleritis was diffuse in 49, nodular in 28, necrotizing in 6, and posterior in 2 patients. Anterior uveitis (4% vs 31%; p<0.006), peripheral ulcerative keratitis (0% vs 14%; p<0.167), ocular hypertension (0% vs 7%; p<0.333), and a decrease in visual acuity (4% vs 19%; p<0.112) were encountered as ocular complications in patients with episcleritis and patients with scleritis, respectively. An associated systemic disease was found in 20% and 52% of patients with episcleritis and patients with scleritis (p<0.004). Among patients with episcleritis, 76% required topical corticosteroid treatment to achieve disease resolution, 16% oral nonsteroidal anti-inflammatory drugs (NSAIDs), and 8% antivirals; 39% of patients with scleritis required systemic NSAIDs, 12% oral corticosteroids, 34% immunosuppressive drugs, and 15% antibiotics or antivirals. Conclusions The importance of differentiating scleritis from episcleritis is remarkable given the significant difference in the degree of ocular complications and associated systemic diseases between these ocular conditions. Prompt diagnosis, systemic assessment, and treatment are fundamental in all patients with scleral inflammation.

Intravitreal bevacizumab for nonsubfoveal choroidal neovascularization associated with angioid streaks.

PURPOSE To evaluate the effects of intravitreal bevacizumab injections in the treatment of nonsubfoveal choroidal neovascularization (CNV) associated with angioid streaks. DESIGN Nonrandomized, interventional, prospective case series. METHODS Fifteen patients (15 eyes) affected by juxtafoveal or extrafoveal CNV secondary to angioid streaks were enrolled in the study. All patients underwent a complete ophthalmologic examination, including best-corrected visual acuity (BCVA) measurement on Early Treatment Diabetic Retinopathy Study (ETDRS) chart, optical coherence tomography (OCT), and fluorescein angiography (FA). The protocol treatment included a first injection, followed by repeated injections over a 12-month follow-up period on the basis of the detection of new hemorrhage on biomicroscopic examination, any type of fluid on OCT, or presence of leakage on FA. PRIMARY OUTCOME MEASURES Mean changes in BCVA and proportion of eyes gaining at least 10 letters (2 ETDRS lines) at the end of the follow-up. SECONDARY OUTCOMES Mean changes of central macular thickness (CMT) and extension to the fovea. RESULTS Mean BCVA did not change throughout the follow-up period, being 0.2 ± 0.2 logMAR at baseline and 0.2 ± 0.3 logMAR at the 12-month examination. A functional improvement of at least 2 ETDRS lines was achieved by 5 eyes (33%), with 3 eyes (20%) gaining 3 lines. Mean CMT at baseline was 215 ± 13 μm and 225 ± 85 μm at the 12-month examination. Two eyes (13.3%) showed CNV extension to the fovea. CONCLUSIONS Intravitreal bevacizumab injection can be a beneficial approach for the management of nonsubfoveal CNV secondary to angioid streaks over a 1-year follow-up.

DYNAMIC AND STATIC RETINAL VESSEL ANALYSES IN PATIENTS WITH MACULAR EDEMA SECONDARY TO RETINAL VEIN OCCLUSION.

Purpose: To investigate the vasomotor responses and diameter of retinal vessels in patients with macular edema secondary to retinal vein occlusion (RVO). Methods: A total of 18 eyes of 18 RVO patients were consecutively included and compared with age- and sex-matched controls. Participants underwent an examination with optical coherence tomography and dynamic and static retinal vessel analyses using the Dynamic Vessel Analyzer. Results: Dynamic vessel analysis in RVO showed mean maximum venous and arterial dilation of 2.22 ± 1.23% and 1.87 ± 1.41%, respectively, as compared with 5.05 ± 2.75% (P = 0.001) and 3.95 ± 1.44% (P = 0.0004), respectively, in controls. Static retinal vessel analysis in RVO revealed a mean arteriovenous ratio (AVR) of 0.74 ± 0.09 versus 0.90 ± 0.04 (P < 0.0001) in controls. Mean AVRs of occluded and nonoccluded quadrants in RVO were 0.71 ± 0.13 and 0.85 ± 0.19, respectively; in the corresponding quadrants of controls, mean AVRs were 0.90 ± 0.19 (P < 0.0001) and 0.86 ± 0.17 (P = 0.89), respectively. In branch RVO patients, mean AVRs of occluded versus nonoccluded quadrants were 0.70 ± 0.06 and 0.90 ± 0.22 (P = 0.002), respectively. Conclusion: In patients with macular edema secondary to RVO, dynamic vessel analysis showed an impairment of both venous and arterial motility and/or reactivity and static vessel analysis showed a reduced AVR indicating a general enlargement of the retinal venous network. Moreover, in branch RVO patients, static analysis demonstrated that retinal vessels could actually be uninvolved by the occlusive process in areas spared by disease.

Morpho-functional correlation of fundus autofluorescence in Stargardt disease

Background To correlate patterns in short-wavelength (SW) and near-infrared (NIR) fundus autofluorescence (FAF) with morpho-functional outcomes in eyes affected by Stargardt disease. Methods Fifty-four eyes of 27 patients were prospectively enrolled. All patients underwent a complete ophthalmologic examination including SW-FAF, NIR-FAF, microperimetry and spectral-domain optical coherence tomography (SD-OCT). The main outcome measures were identification of a correlation between NIR-FAF and SW-FAF patterns within the foveal region and best corrected visual acuity (BCVA) values. Secondary outcome measures were correlation of FAF patterns with SD-OCT findings and retinal sensitivity on microperimetry. Results Eyes showing a pattern of foveal hyper-FAF on NIR-FAF had a higher BCVA than eyes with a reduced FAF signal (0.44±0.23 LogMAR vs 1.08±0.19, p<0.001). Similarly, mean sensitivity within 2° of the foveal region was significantly better (6.45±2.39 dB) in eyes with hyper-FAF than in eyes with hypo-FAF (0.23±0.45 dB, p<0.001). Moreover, eyes with hyper-FAF on SW-FAF did not present a significant difference in BCVA (0.73±0.31 vs 0.83±0.43, p=0.335) and mean retinal sensitivity (4.34±3.91 dB vs 2.33±2.96, p=0.07) compared with the subgroup with foveal hypo-FAF. The integrity of both the photoreceptor inner/outer segment junction and the photoreceptor outer segment/retinal pigmented epithelium junction was significantly correlated with a preserved BCVA and a foveal hyper-FAF pattern on NIR-FAF. Conclusions Our data suggest that NIR-FAF patterns correlate with morpho-functional outcomes in eyes affected by Stargardt disease. Longitudinal investigations are warranted to assess more precisely the actual contribution of NIR-FAF in the clinical characterisation of Stargardt disease.

Stereo tests as a screening tool for strabismus: which is the best choice?

Purpose To compare four stereo tests (Lang I, Lang II, Titmus, and TNO) and assess their effectiveness. The main focus of this study is to identify the most useful stereo test as a challenging tool in the screening of strabismus. Patients and methods A total of 143 Caucasian subjects, 74 males (52%) and 69 females (48%), aged between 4 years and 78 years (mean age 19.09±15.12 years) were examined at our Strabismus Service (Scientific Institute San Raffaele Hospital, Milan, Italy) and included in this observational cross-sectional study. Subjects recruited in this study were either affected by strabismus, including microstrabismic patients, or healthy volunteers. Subjects affected by ophthalmological diseases, other than strabismus, were excluded. All patients underwent both ophthalmological and orthoptic examination, including stereo tests, Hirschberg Corneal Light Reflex Test, Worth Four-Dot Test, the 4 Prism Diopter Base-Out Test, Cover Testing, Bruckner Test, visual acuity, automated refraction under 1% tropicamide cycloplegia and thereafter, posterior pole evaluation. Results All data were processed using the IBM SPSS Statistics, Version 2.0, to perform all statistical calculations. The main finding of this study is that Lang I stereo test achieved the highest sensitivity (89.8%) and specificity (95.2%) in detecting strabismus, including microstrabismus as well, compared to all the other stereoacuity tests. Furthermore, Lang I is the stereo test with the highest positive predictive value and negative predictive value, both greater than 90%. Conclusion The stereo test with the highest sensitivity, specificity, positive predictive value, and negative predictive value is Lang I. These results suggest its applicability as a screening test for strabismus in people older than 4 years.

Optical coherence tomography angiography findings in laser maculopathy

Purpose Handheld laser pointer thermal injury affects primarily the retinal pigment epithelium (RPE). However, so far no study has reported on the possible effects of laser pointers in the deeper layers, beneath the RPE. Here, we describe the spectral-domain optical coherence tomography angiography findings in the choriocapillaris of a patient with laser maculopathy. Methods A 13-year-old boy presented to our department with decreased vision in the left eye 12 hours after having stared at the beam of a laser pointer. Results Structural optical coherence tomography (OCT) showed 2 focal hyperreflective columns at the fovea extending from the RPE, involving all outer retinal layers, and terminating at the outer plexiform layer. The patient also underwent OCT angiography (OCT-A), which in the choriocapillary segmentation revealed 2 hypointense lesions in correspondence of the focal hyperreflectivities detected on structural OCT. We hypothesize that the OCT-A findings could represent a rarefaction of the choriocapillaris. However, the choriocapillary OCT-A findings could also represent artifacts due to the overlaying hyperreflective lesions. Conclusions It is known that the RPE is primarily damaged by the laser injury. Our findings suggest that the thermal injury could involve also the choriocapillaris, and thus not limited to the RPE. Multimodal imaging in laser maculopathy including OCT-A may lead to a better comprehension of the pathogenesis of laser retinal damages.