Anatomical and functional changes in neovascular AMD in remission: comparison of fibrocellular and fibrovascular phenotypes.

PURPOSE: To investigate the anatomical changes and the macular function in neovascular age-related macular degeneration (AMD) eyes, according to the recognition of either fibrocellular or fibrovascular phenotype. METHODS: We enrolled eyes with previously treated neovascular AMD in remission (no subretinal haemorrhage, sign of fluid in or under the retina and no treatment for at least 6 months). Subjects underwent multimodal imaging assessment and were tested for macular sensitivity using microperimetry. The study cohort was divided according to the presence of fibrosis on multicolour (MC) images, yielding two distinct phenotypic subgroups: (1) fibrocellular group and (2) fibrovascular group. RESULTS: Nineteen eyes were classified as fibrocellular on MC images, while 22 eyes as fibrovascular. Mean±SD age was 73.9±11.0 years in the fibrocellular group and 75.9±7.1 years in the fibrovascular group (p=0.221). Best-corrected visual acuity was 0.7±0.5 logarithm of the minimum angle of resolution (LogMAR) in the fibrocellular group and 0.3±0.2 LogMAR in the fibrovascular group (p=0.003). On the optical coherence tomography and fundus autofluorescence evaluation, 17/19 eyes with the fibrocellular phenotype and 8/22 eyes with the fibrovascular phenotype displayed the presence of retinal pigment epithelium (RPE) atrophy (p=0.001). The perfusion density within the neovascular lesion was 28.9%±9.9% in the fibrocellular group and 44.2%±5.9 % in the fibrovascular group (p<0.0001). CONCLUSION: Neovascular AMD eyes in remission and with evidence of fibrocellular scar are characterised by RPE atrophy and reduced perfusion, which are associated with a higher degree of functional impairment. These findings suggest that maturation of vessels in fibrosis might be a better target in neovascular AMD treatments rather than their abolishment.

CHRONIC CENTRAL SEROUS CHORIORETINOPATHY: Early and Late Morphological and Functional Changes After Verteporfin Photodynamic Therapy.

PURPOSE: To describe early and late morphological and functional changes in subjects receiving photodynamic therapy (PDT) for chronic central serous chorioretinopathy. METHODS: Patients with chronic central serous chorioretinopathy were prospectively enrolled and received standard PDT. At the baseline examination, each subject underwent complete ophthalmological examination, including best-corrected visual acuity (BCVA) assessment, fluorescein angiography and indocyanine green angiography, spectral domain optical coherence tomography, and microperimetry. Spectral domain optical coherence tomography, microperimetry, and BCVA assessment were repeated in multiple sections over 7 days after PDT and at 1-, 3-, and 12-month intervals. Main outcome measures were: identification of early changes (1-week examination) in BCVA, retinal sensitivity, and spectral domain optical coherence tomography parameters and their influence on outcomes at the 1-year follow-up. RESULTS: Three main patterns of early response to PDT were identified during the 1-week examination. The neurosensory retinal detachment most frequently decreased rapidly (12/19 pts), with complete resolution in 50% of cases. An increase in neurosensory retinal detachment height was registered in 16% (3/19) of cases, whereas in 21% (4/19), a large fluctuation in neurosensory retinal detachment was encountered. Best-corrected visual acuity declined significantly in 5/12 patients in the first group and was stable or improved in the remaining cases. Overall, retinal sensitivity diminished in 16/19 subjects, with a mean worsening of 2.56 dB (P = 0.0002). At the 12-month examination, final mean BCVA improved by 14.4 letters (P = 0.001) and a similar progressive recovery in the retinal sensitivity was observed (+2.69 dB, P = 0.0039). The neurosensory retinal detachment completely resolved in 18/19 (95%) cases, with a parallel significant reduction in central foveal choroidal thickness (P < 0.0001). CONCLUSION: Three patterns of early response to standard PDT can be identified. Although an early and abrupt reduction in BCVA and retinal sensitivity after treatment is possible, this does not compromise a final improvement in visual functions.

FACTORS INFLUENCING VISUAL ACUITY IN PATIENTS RECEIVING ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR FOR MYOPIC CHOROIDAL NEOVASCULARIZATION.

PURPOSE: To identify the prognostic variables relative to myopic choroidal neovascularization (CNV) treated with intravitreal ranibizumab/bevacizumab. METHODS: Forty-eight patients with myopic CNV were enrolled in a prospective, interventional, non-randomized 12-month study. Intravitreal ranibizumab/bevacizumab was administered in a pro-re-nata regimen and re-treatment was performed in the presence of angiographic leakage, intraretinal/subretinal fluid on optical coherence tomography, new hemorrhages, five-letter decrease and increased metamorphosia. The primary outcome measures were the identification of the predictive value of symptom duration, patient's age, refractive error, best-corrected visual acuity (BCVA), central macular thickness (CMT), CNV area, CNV location, retinal hemorrhages, atrophy, lacquer cracks, and CNV-fundus autofluorescence pattern (hyper-fundus autofluorescence/patchy pattern). The secondary outcomes were patients requiring either one or two injections to achieve CNV stabilization. RESULTS: The mean BCVA improved from 0.49 ± 0.30 (logarithm of minimal angle resolution, Snellen equivalent 20/63) to 0.39 ± 0.32 (20/49) at 1-year follow-up (P = 0.043). Univariate and multiple stepwise linear regression analysis identified baseline BCVA (P = 0.0003), symptom duration (P = 0.005), CMT (P = 0.02), and fundus autofluorescence pattern (P = 0.005) as the explanatory variables on the final BCVA and the change in the mean BCVA. Overall, patients with better baseline BCVA, early diagnosis, lower CMT, or disclosing a hyperfundus autofluorescence CNV pattern achieved better visual outcomes. Patients responding with just one to two intravitreal injections (45.8%) obtained better visual outcomes compared with patients receiving three or more injections, and this group consisted of younger patients with lesser CMT, smaller CNV area, and fewer baseline hemorrhages. CONCLUSION: Ranibizumab/bevacizumab therapy was effective in improving and maintaining visual acuity in myopic choroidal neovascularization. Early diagnosis, better baseline BCVA, and hyperfundus autofluorescence CNV pattern were strongly associated with better functional outcomes. Moreover, CNV distinguished by its small size and low CMT responded more favorably, achieving a better visual outcome.

Exploring the morphological and functional retinal changes after dexamethasone intravitreal implant (Ozurdex®) in macular edema due to retinal vein occlusion.

PURPOSE: To explore functional and morphological retinal changes 6 months after dexamethasone intravitreal implant (DEX implant) for the treatment of macular edema due to central or branch retinal vein occlusion (CRVO, BRVO). PROCEDURES: In this prospective interventional case series patients underwent a complete ophthalmological examination at baseline and monthly, including best-corrected visual acuity (BCVA), spectral domain-optical coherence tomography and microperimetry. Fluorescein angiography was performed at baseline and at 4 months. All patients were treated with a DEX implant and retreated according to predefined criteria starting from month 4. RESULTS: Sixteen patients (mean age 66 ± 13 years, 14 CRVO, 2 BRVO) were included. At 6 months mean retinal sensitivity improved from 9.7 ± 4.6 to 13.6 ± 5.4 dB (p < 0.0001) while mean BCVA improved from 52.4 ± 16.2 to 66.1 ± 16.6 (p < 0.0001). Mean central retinal thickness decreased from 708.3 ± 151.01 to 362.7 ± 177.4 µm (p < 0.0001); 56.2% of eyes were retreated at month 4. CONCLUSIONS: At 6 months DEX implant led to a significant improvement in retinal sensitivity and visual acuity associated with a reduction of retinal thickness in patients with macular edema due to retinal vein occlusion.

Photodynamic therapy in subfoveal and juxtafoveal myopic choroidal neovascularization: a 10-year retrospective analysis.

The aim of this study was to evaluate and compare the effects of photodynamic therapy (PDT) in eyes with subfoveal and juxtafoveal choroidal neovascularization (CNV) secondary to pathological myopia. The study was a single-center, 10-year analysis on 19 eyes. Patients underwent best-corrected visual acuity (BCVA) measurement, slit-lamp examination, ophthalmoscopy and fluorescein angiography. Eyes with subfoveal CNV (7 eyes, 37%) progressively worsened during the 10-year follow-up from 0.68 ± 0.26 to 0.80 ± 0.47 logMAR, while in the eyes with juxtafoveal CNV (12 eyes, 63%) BCVA improved from 0.59 ± 0.42 to 0.33 ± 0.27 logMAR. Prevalence and extension of chorioretinal atrophy (CRA) were greater in eyes with subfoveal compared with juxtafoveal CNV (84 vs. 66%, respectively) and enlargement (10.05 ± 6.7 vs. 3.53 ± 4.7 mm(2), respectively). Our results confirm the limited long-term effectiveness of PDT in myopic subfoveal CNV. Satisfactory results can be achieved in juxtafoveal CNV with a better visual outcome and a minor CRA extension.

Single-session photodynamic therapy combined with intravitreal ranibizumab for neovascular age-related macular degeneration: a comprehensive functional retinal assessment.

PURPOSE: To explore functional retinal changes in neovascular AMD patients (nAMD) treated with ranibizumab 0.5 mg combined with photodynamic therapy (PDT) 3 days after the first injection in the long term. METHODS: Patients with no prior treatment for nAMD were treated with 3 injections of ranibizumab 0.5 mg 1 month apart and a single session of standard PDT 3 days after the first injection. Best-corrected visual acuity and time-domain OCT at baseline and every 28 ± 2 days were performed; microperimetry at 3, 6, and 12 months and multifocal electroretinogramm (mfERG) at 3 and 12 months were repeated. Fluorescein angiography and vision-related quality-of-life questionnaire were performed at baseline and 12 months. RESULTS: 12/15 nAMD patients completed the 12 months study and received an average of 3.4 ± 0.7 injections. Mean VA changed from 54.67 ± 15.72 to 59.0 ± 24.77 letters (p = 0.371), while mean retinal sensitivity from 5.5 ± 4.8 to 6.6 ± 6.0 dB (p = 0.216). MfERG N1-P1 response amplitude densities (RADs) were significantly different from baseline (p < 0.01) in the central 0°-2.5°, whereas in the peripheral retinal areas (2.5°-20°), not significant (p > 0.01) changes in N1-P1 RADs were detected. The "general vision" VFQ-25 subscale showed a statistically significant improvement at 3 and 12 months. CONCLUSIONS: Ranibizumab 0.5 mg combined with standard PDT 3 days after the first injection determines an improvement of mfERG values in the retinal central area in nAMD patients in long-term follow-up.

Functional and structural assessment of lamellar macular holes.

AIM: The purpose of the present work was to evaluate the macular sensitivity of patients with lamellar macular hole (LMH) by means of microperimetry, and to explore the relationships between macular function, LMH anatomical characteristics and vitreous status. METHODS: A total of 39 eyes from 37 patients with a diagnosis of LMH and 20 age-matched control subjects were enrolled. All patients underwent a complete ophthalmological examination including visual acuity testing (logMAR) and MP1 microperimetry. LMHs were quantitatively and qualitative characterised by spectral domain optical coherence tomography (OCT) in terms of base and apex diameter, depth, central foveal and perifoveal thickness, splitting location and integrity of outer retina layers. B scan ultrasonography was performed in order to characterise the vitreoretinal relationships. RESULTS: Mean total (17.2 ± 2.2 vs 19.6 ± 0.5 dB, respectively, p<0.0001) and mean central (16.1 ± 3.2 vs 19.2 ± 0.7 dB, p < 0.0001) retinal sensitivity were significantly reduced in LMH eyes in comparison with controls. Best corrected visual acuity (BCVA) (0.15 ± 0.15 vs 0.03 ± 0.06 logMar, p = 0.001) and central retinal thickness (329.05 ± 59.3 vs 265 ± 28.5 µm, p < 0.0001) were significantly worse in LMH eyes in comparison with controls. In our population, mean total and central retinal sensitivity showed a moderately significant relationship with LMH depth (R(2) 0.18, p = 0.006, R(2) 0.14, p = 0.02, respectively). In all, 38% of LMH eyes (15/39) showed focal interruptions of the inner-outer segment junction with lower values of BCVA and macular sensitivity. An incomplete posterior vitreous detachment with vitreopapillary adhesion was found in 48.7% (19/39) of patients with LMH. CONCLUSIONS: Eyes with LMH show an impaired macular function, which is partially related to LMH depth and is more pronounced in eyes with outer retinal layers abnormalities.

Foveal microstructure and functional parameters in lamellar macular hole.

PURPOSE: To evaluate the morphologic features of the photoreceptor layer (by spectral-domain optical coherence tomography) and functional parameters in patients with a lamellar macular hole. DESIGN: Prospective, multicenter, observational case series. METHODS: Fifty-four patients with lamellar macular hole were enrolled in the study. All patients underwent a complete ophthalmologic examination, including best-corrected visual acuity (BCVA) testing, MP1 microperimetry, and spectral-domain optical coherence tomography. For each patient, 2 experienced masked observers evaluated the integrity of photoreceptor inner segment/outer segment (IS/OS) junction and external limiting membrane (ELM) line. RESULTS: Spectral-domain optical coherence tomography analysis showed complete integrity of the IS/OS junction and ELM line in 40 eyes (group A), partial or complete disruption of the IS/OS junction with an intact ELM line in 8 eyes (group B), and an alteration of both IS/OS junction and ELM line in 6 eyes (group C). Mean BCVA, total retinal sensitivity, and fixation stability were significantly better in groups A and B than in group C (both P < .05, Tukey-Kramer test), whereas there was no significant difference between groups A and B. Mean central retinal sensitivity was significantly different among all 3 groups (all P < .05, Tukey-Kramer test). The grade of integrity of the foveal photoreceptor layer was correlated significantly with mean BCVA (r = -0.57; P < .001), mean central retinal sensitivity (r = 0.52; P < .001), and total retinal sensitivity (r = 0.44; P < .001). CONCLUSIONS: In lamellar macular hole, the morphologic features of the foveal photoreceptor layer consistently are correlated with BCVA and central retinal sensitivity. Preservation of the ELM is related to the maintenance of visual acuity.

Reproducibility of macular thickness measurements using Cirrus SD-OCT in neovascular age-related macular degeneration.

PURPOSE: To assess the test-retest variability of central and sectorial macular thickness measurements obtained by Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) in neovascular age-related macular degeneration (nAMD). METHODS: Macular thickness measurements of nine standard ETDRS subfields were obtained and analyzed. The repeatability of macular thickness measurements by Cirrus HD-OCT was assessed by examining the intrasession within subject standard deviation (Sw), coefficient of repeatability (CR), and coefficient of variation (CV), before and after eyes with retinal segmentation errors were excluded. RESULTS: Forty-nine nAMD eyes of 49 consecutive patients were included in the study. The CR for the central macular subfield was 42.4 microm (10.5%) and ranged from 12.1 microm (3.7%) for the outer nasal to 41.8 microm (11.4%) for the inner nasal subfields. In a secondary analysis, eyes affected by erroneous detection of inner and outer retinal boundaries (6/49, 12.24%) were excluded. The revised coefficient of repeatability for the central macular subfield was 26.1 microm (8.1%) and ranged from 10.3 microm (3.8%) for the outer superior to 30.2 microm (8.3%) for the inner nasal subfields. CONCLUSIONS: Overall, the test-retest variability of Cirrus HD-OCT is good for the central and sectorial macular subfields, with a low incidence of scan artifacts.

Retinal functional changes measured by microperimetry in neovascular age-related macular degeneration treated with ranibizumab: 24-month results.

PURPOSE: The purpose of this study was to assess long-term functional and structural retinal changes in patients with neovascular age-related macular degeneration treated with intravitreal 0.5 mg ranibizumab. METHODS: Eighteen patients with neovascular age-related macular degeneration have been evaluated in this retrospective 24-month follow-up study. All patients have been treated with 3 injections of 0.5 mg ranibizumab 1 month apart and retreated according to predefined criteria. At baseline, all patients were subjected to visual acuity, fluorescein angiography, MP1 microperimetry, and Stratus optical coherence tomography. Although visual acuity and optical coherence tomography were repeated 28 +/- 2 days after each injection, MP1 was performed at 6, 12, and 24 months. RESULTS: Seventeen of 18 and 14 of 18 patients completed 12 and 24 months of follow-up, respectively. Mean retinal sensitivity significantly improved from 3.89 +/- 3.0 dB to 7.33 +/- 4.11 dB at 24 months (P = 0.024). Mean visual acuity improved from 48.67 +/- 8.59 to 59.17 +/- 16.45 at 24 months (P = 0.049). Visual acuity improved to >or=15 letters in 33.3% (6 of 18) of patients and <15 letters in 44.4% (8 of 18); 22.2% (4 of 18) of patients lost <15 letters at 24 months. Five of 13 patients (38.5%) with either an instable or relatively instable fixation at baseline showed improvement of fixation stability at 24 months. Central retinal thickness significantly decreased from 310.5 +/- 85.7 to 232.9 +/- 60.1 at 24 months (P = 0.0001). CONCLUSION: Intravitreal injections of 0.5 mg ranibizumab determine progressive improvement of retinal sensitivity until 24 months, although visual acuity levels off after 6 months, suggesting that microperimetry may give additional information about macular function not given by visual acuity alone.

Retinal functional changes measured by microperimetry in neovascular age-related macular degeneration patients treated with ranibizumab.

PURPOSE: To assess functional and structural retinal changes in patients with neovascular age-related macular degeneration treated with intravitreal ranibizumab 0.5 mg. METHODS: Eighteen patients with neovascular age-related macular degeneration have been evaluated in this retrospective 24-week follow-up study. All patients were treated with three injections of ranibizumab 0.5 mg, 1 month apart and retreated according to predefined criteria. At baseline, all patients were subjected to visual acuity measurement, fluorescein angiography, microperimetry, and optical coherence tomography stratus. Visual acuity, microperimetry, and optical coherence tomography evaluations were repeated 28 +/- 2 days after each injection. RESULTS: Mean retinal sensitivity significantly improved from 3.89 +/- 3.0 dB at baseline to 6.61 +/- 3.4 dB at 24 weeks (P = 0.044). Mean visual acuity significantly improved from 48.67 +/- 8.58 to 60.72 +/- 16.09 (P = 0.026); visual acuity improved in 44.4% of patients > or =15 letters (24.5 +/- 8.0 letters), and in 38.9% of patients improved <15 letters (6.14 +/- 3.7 letters); 16.7% of patients lost <15 letters (7.3 +/- 2.1 letters). An improvement of fixation stability from baseline was observed in 33.3% of patients. Central macular thickness significantly decreased from 310.5 +/- 85.7 microm to 217.3 +/- 46.8 microm at 24 weeks (P < 0.001). CONCLUSIONS: Although visual acuity and retinal thickness changes seemed to be almost maximum at 4 weeks after intravitreal ranibizumab 0.5 mg, retinal sensitivity as measured by microperimetry showed a trend of progressive improvement till 24 weeks suggesting that microperimetry may give additional information about macular function not given by visual acuity alone.

Posterior vitreous detachment and retinal detachment after cataract surgery.

OBJECTIVE: To evaluate possible changes of vitreous status in emmetropic eyes after uneventful phacoemulsification surgery, and possible related complications such as the onset of retinal detachment (RD). DESIGN: Retrospective case series. PARTICIPANTS: Four hundred fifty-three emmetropic eyes from 453 patients (mean age, 62.03+/-5.57 years) subjected to uneventful phacoemulsification with intraocular lens implantation in the capsular bag were considered in the study. They had a refractive error within +/-0.5 diopters (mean, -0.21+/-0.08). Eyes with peripheral retinal lattice degeneration were included only if asymptomatic and only if the degeneration involved one retinal quadrant. After cataract surgery, the 453 eyes were evaluated preoperatively at days 1, 15, and 30 and months 3, 6, 12, 18, 24, 36, 48, and 60. The whole period of follow-up was 5 years. METHODS: Evaluation of vitreous status by biomicroscopic examination, indirect binocular ophthalmoscopy, and B-scan ultrasonography. MAIN OUTCOME MEASURES: Postoperative onset of posterior vitreous detachment (PVD) and RD. RESULTS: After cataract surgery, a PVD occurred in 107 of 141 (75.88%) eyes without preoperative PVD or lattice degeneration. Posterior vitreous detachment occurred in 41 of 47 eyes (87.23%) with preoperative lattice degeneration and no PVD. Eyes with preoperative lattice degeneration and postoperative PVD showed a higher incidence of RD after cataract surgery (21.27%) than eyes without preoperative PVD or lattice degeneration (0.70%). In all patients with lattice degeneration, RD originated from horseshoe retinal tears on lattice areas located on the superior quadrants. No correlation was observed between the development of RD and age. CONCLUSIONS: Our results suggest that the onset of postoperative PVD should be considered an important risk factor for the development of RD after cataract surgery, particularly in eyes with lattice areas.