Decreased peri-parafoveal RPE, EZ and ELM intensity: A novel predictive biomarker for hydroxychloroquine retinal toxicity.

PURPOSE: To evaluate the reflectivities of the retinal pigment epithelium (RPE), ellipsoid zone (EZ), and external limiting membrane (ELM) in the central fovea, perifoveal, and parafoveal regions with Optical Coherence Tomography (OCT) and the change in choroid vascular index (CVI) in patients using hydroxychloroquine (HCQ). METHODS: Sixty-one patients underwent HCQ treatment; age and sex-matched 44 control group subjects were included in the study. The RPE, EZ, and ELM reflectivities were measured with the ImageJ program at 5 points, and CVI was calculated. RESULTS: RPE, EZ, and ELM reflectivities in the central fovea were higher in the HCQ group than in the control group (p < 0.001, p = 0.013, p = 0.022). In the HCQ group, there was a decrease in RPE reflectivities in the temporal, nasal parafovea, and nasal perifovea (p = 0.001, p = 0.03, p = < 0.001). EZ and ELM reflectivity in the nasal parafovea and nasal perifovea was lower in the patient group than in the control group (p = 0.007, p = 0.005, p = 0.009, p = 0.001). In the HCQ group, all absolute para and perifoveal reflectivities relative to the fovea decreased significantly more than in the control group (p < 0.05). CONCLUSION: In patients who underwent HCQ treatment, there is a decrease in the reflectivities of the para and perifoveal RPE, EZ, and ELM compared to the fovea. This decrease is more pronounced than the decrease in reflectivity in the para and perifoveal regions compared to the fovea in people who do not use HCQ. This situation can be considered as a sign of toxicity that is a precursor to overt maculopathy.

Changes in foveal photoreceptor integrity after idiopathic epiretinal membrane surgery and its relationship with visual outcomes.

PURPOSE: To investigate the changes in the external limiting membrane (ELM), ellipsoid zone (EZ), and interdigitation zone (IZ) integrity and their relationship with visual outcomes after idiopathic epiretinal membranes peeling. METHODS: Clinical records of 150 eyes from 144 consecutive patients who underwent vitrectomy were reviewed. The status of IZ, EZ, and ELM was assessed by spectral-domain optical coherence tomography at baseline and 1, 4, 10, and 24 months postoperatively. RESULTS: Sixty-one eyes presented with photoreceptor layer disruption preoperatively, and IZ disruption (40.7%) was the primary type. The best-corrected visual acuity (BCVA) in the photoreceptor disruption group was significantly lower than that in the intact group at baseline and the final follow-up. Of them, ELM + EZ + IZ disruption showed the worst BCVA (P = 0.001). After surgery, 62 eyes were observed with disruption aggravated. EZ + IZ disruption (51.0%) was the most frequent type at 1 month postoperatively. The eyes with longer symptom duration, better BCVA, earlier stage, thinner CFT at baseline, and combined cataract surgery more tended to be observed with photoreceptor damage progressed after surgery (P < 0.05). There was no significant difference in the final BCVA between the eyes with and without damage progressed (P = 0.332). Finally, 28.1% of the eyes recovered photoreceptor continuity. The eyes with foveal photoreceptor integrity restored had better BCVA than those remaining discontinuous (P < 0.001). CONCLUSION: ERM-induced photoreceptor disruption mainly manifests as IZ disruption and has a negative effect on BCVA, whereas surgery mainly causes EZ and IZ disruption, which does not have a significant impact on the final BCVA.

Visual improvement and regeneration of retinal layers in eyes with small, medium, and large idiopathic full-thickness macular holes treated with the inverted internal limiting membrane flap technique over a period of 12 months.

PURPOSE: This study aims to compare the improvement of best-corrected visual acuity (BCVA) and the reduction in defect length of external limiting membrane (ELM) and ellipsoid zone (EZ) in small ([Formula: see text] 250 µm), medium ([Formula: see text] 250 µm), and large ([Formula: see text] 400 µm) full-thickness macular holes (FTMH) treated with inverted internal limiting membrane (I-ILM) flap technique over a follow-up period of 12 months. METHODS: Ninety-one eyes of 87 patients were enrolled in this retrospective study. BCVA and spectral-domain optical coherence tomography (SD-OCT) were conducted preoperatively as well as after 1, 3, 6, 9, and 12 months postoperatively. The defect length of the ELM and the EZ was measured using the caliper tool at each follow-up time point. RESULTS: BCVA improved significantly in the group of small, medium, and large FTMH over the time of 12 months, whereby the improvement did not depend on FTMH size over 9 months. Only after 12 months, large FTMH showed significantly higher BCVA improvement compared to small and medium FTMH. The closure rate was 100% (91/91). The defect length of ELM and EZ reduced continuously over the period of 12 months. There was a significant correlation between defect length of ELM and EZ with postoperative BCVA. CONCLUSION: The I-ILM flap technique has very good morphological and functional outcomes in small, medium, and large FTMH over a long-time period, indicating that it can be considered as a treatment option in small and medium FTMH. The defect length of ELM and EZ is directly connected to postoperative BCVA.

Recovery course of foveal microstructure in the nonsurgical resolution of full-thickness macular hole.

PURPOSE: To analyze the recovery course of foveal microstructures in eyes with nonsurgical healing of full-thickness macular hole (FTMH). METHODS: By serial OCT scans, the temporal healing sequences were analyzed in ocular trauma, vitreomacular traction (VMT), cystoid macular edema (CME), and the remaining group. We evaluated correlations between the final best-corrected spectacle visual acuity and reconstruction time of external limiting membrane (ELM), and inner segment/outer segment (IS/OS). RESULTS: The healing (mean±standard deviation in months) most involved fusion at the level of the outer nuclear layer (ONL) (6.3±10.5) followed by restoration of ELM (9.1±13.8), and lastly, by IS/OS regeneration (13.1±19.5). In severe blunt ocular trauma, healing was fast and involved subretinal zipper glue-like reapposition with resulting outer retinal atrophy. Best spectacle-corrected visual acuity correlated with normalization of the clivus (p=0.012), faster ELM (p=0.006), and IS/OS reconstitution (p=0.024). Recurrence of FTMH occurred when the healing was halted (3 eyes) or was aberrant by lamellar hole epiretinal proliferation (LHEP) (3 eyes) or by the persistence of VMT (1 eye). CONCLUSION: Recovery sequences proceeded from the ONL to the deeper layers with BCVA correlating absolutely and temporally with the restoration of outer retinal layer integrity.

Correlating optical coherence tomography biomarkers with visual acuity in nigerian retinitis pigmentosa patients.

Background: Spectral Domain Optical Coherence Tomography (SD-OCT) has been used for imaging retinitis pigmentosa (RP) eyes and provides useful information on microstructural changes. Aim: To review SD-OCT findings and correlate the central foveal thickness (CFT), outer nuclear layer (ONL), external limiting membrane (ELM), and ellipsoid zone (EZ) with visual function in nonsyndromic RP eyes. Patients and Methods: A multicenter, retrospective review of records from consecutive eyes diagnosed to have RP. Biodata, systemic disease, visual acuity, lens status, intraocular pressure, and SD-OCT images were examined. The CFT was categorized into normal (250-299 microns), atrophic (0-249 microns), and edematous (≥300 microns). The ONL, ELM, and EZ within the subfoveal area was assessed and rated as normal, reduced (if less than normal), or absent (if missing). The status of these biomarkers was correlated with visual acuity and statistical analysis performed using Pearson Chi2, P < 0.05. In addition, the vitreomacular interface was examined for the presence of vitreomacular traction (VMT), vitreomacular adhesion (VMA), and epiretinal membrane (ERM). Results: Fifty-two RP eyes of 27 patients had SD-OCT images that were used for study analysis. There were 17 males and 10 females; 52% of participants were between 31 and 50 years (age range: 22-77 years). An atrophic retina was the most common finding in 42 eyes (81%); the average CFT in the atrophic group was 175 microns (range: 111-245 microns). There were three eyes with cystoid macular edema, and seven eyes were normal. For the OCT biomarkers, a reduction in ONL and ELM occurred in 69% and 46% of eyes, respectively, while an absence was the most common EZ finding (in 50% of eyes). There was a significant correlation between the presence or absence of the three biomarkers and presenting vision: ONL, ELM, and EZ with P values of 0.000, 0.006, and 0.011, respectively. The CFT had no significant correlation with vision; P = 0.522. Other findings on OCT include ERM 17%, VMA 6%, and VMT 2%. Conclusion: This report supports the notion that OCT image reporting on physical retinal structure in RP eyes can be used to predict disease effects on vision. A prospective study to better quantify the degree of structural change and correlate with the degree of functional loss is required for RP gene types in Nigerians and black Africans.

Inverted internal limiting membrane flap technique in eyes with large idiopathic full-thickness macular hole: long-term functional and morphological outcomes.

PURPOSE: To investigate morphological and functional outcomes of the inverted internal limiting membrane (I-ILM) flap technique in large (≥ 400 µm) idiopathic full-thickness macular holes (FTMH) over a follow-up period of 12 months. METHODS: In this retrospective study, 55 eyes of 54 consecutive patients were enrolled. Best-corrected visual acuity (BCVA) and spectral-domain optical coherence tomography (SD-OCT, Heidelberg, Spectralis) were performed preoperatively as well as 1, 3, 6, 9, and 12 months postoperatively. Special focus was put on the reintegration of outer retinal layers and the different ILM flap appearances. RESULTS: FTMH closure rate was 100% (55/55). BCVA significantly improved over the follow-up period of 12 months from 0.98 ± 0.38 LogMAR preoperatively to 0.42 ± 0.33 LogMAR at 12 months postoperatively (p < 0.001). There was no significant correlation between the three different ILM flap appearances and BCVA. Better preoperative BCVA, complete restoration of the external limiting membrane (ELM), higher macular hole index (MHI), and smaller MH base diameter were associated with higher improvement of BCVA. CONCLUSION: Our study highlights the favorable morphological and functional outcomes of the I-ILM flap technique in the short as well as in the long term. While complete ELM restoration revealed to be an important factor for improvement in BCVA, the different postoperative ILM flap appearances seem not to be related to BCVA.

Subretinal leakage of a retinal capillary macroaneurysm - a case report.

BACKGROUND: Report a rare case of retinal capillary macroaneurysm with associated subretinal fluid. CASE PRESENTATION: A 71-year-old male underwent full ophthalmic examination including Optical Coherence Tomography (OCT), Fluorescein Angiography (FA). Fundus examination showed moderate non-proliferative diabetic retinopathy of both eyes with scattered microaneurysms. On initial visit, FA displayed a hyperfluorescent lesion with leakage on late frames in the left eye. OCT revealed the lesion to be spheroid with a hyperreflective wall and hyporeflective lumen in the inner retina, corresponding to a capillary macroaneurysm. Intraretinal cystic fluid surrounded the lesion. On subsequent visit 7 months later, subretinal fluid in the location of the capillary macroaneurysm was noted on OCT. Vision was maintained at 20/30-2 OD, 20/40 OS throughout. No treatment was necessary. CONCLUSION: Subretinal fluid from the capillary macroaneurysm likely developed from its juxtafoveal location and discontinuity of the external limiting membrane (ELM); a barrier preventing flow of intraretinal fluid to the outer retina.

Vitrectomy for diabetic macular edema and the relevance of external limiting membrane.

PURPOSE: To evaluate the relevance of external limiting membrane (ELM) on the visual and morphological results in eyes with diabetic macular edema (DME) that underwent pars plana vitrectomy (PPV) with epiretinal membrane (ERM) and internal limiting membrane (ILM) peeling. METHODS: Medical records of patients with DME who underwent PPV at our unit between January 2017 and December 2019 were reviewed. We assessed preoperative and postoperative best-corrected visual acuity (BCVA), central macular thickness (CMT) using spectral domain OCT (optical coherence tomography). Exclusion criteria were previous PPV; incomplete data; concomitant diseases including retinal vein occlusion, age-related macular degeneration, uveitis; and a follow-up of less than 12 months. The surgeries were performed using 23- or 27-gauge vitrectomy. The ELM was graded depending on its configuration (grade 0 = intact, grade 1 to 3: disruption of varying extent). RESULTS: Ninety-nine eyes were enrolled. The postoperative follow up averaged 23.7 months. The preoperative and final BCVA averaged 0.71 ± 0.28 and 0.52 ± 0.3 logMAR, respectively (p = 0.002). The CMT averaged 515.2 ± 209.1 µm preoperatively and 327 ± 66.1 µm postoperatively (p = 0.001). Eyes with intact ELM (n = 8) had a significantly better BCVA compared to those with ELM disruption (0.28 ± 0.14 vs. 0.7 ± 0.25 logMAR, p = 0.01). The final CMT was similar among the groups (intact ELM: 317 ± 54.6 µm; ELM disruption: 334 ± 75.2, p = 0.31). CONCLUSIONS: PPV with ERM and ILM peeling is an effective treatment of DME. Eyes with intact ELM preoperatively had a significantly better final visual outcome. To maximize the benefit for patients with DME we recommend early PPV as long as ELM is intact.

Microstructural Macular Changes after Pars Plana Vitrectomy for Primary Rhegmatogenous Retinal Detachment.

PURPOSE: This study aimed to describe foveal microstructural changes after pars plana vitrectomy (PPV) with air tamponade for rhegmatogenous retinal detachment (RRD). METHODS: External limiting membrane (ELM) and ellipsoid zone (EZ) integrity, cystoid macular edema (CME), and subretinal fluid bleb (SB) development were analyzed using optical coherence tomography in 59 eyes over a 6-month follow-up period after PPV surgery for RRD. Eyes were grouped as macula-on (n = 30) or macula-off (n = 29), and the association between ELM and EZ recovery and best-corrected visual acuity (BCVA) was investigated. Predictive factors for ELM and EZ recovery were also identified. RESULTS: The interval between symptom onset and surgery did not significantly differ between the macula-on and macula-off groups. Macula-on patients showed ELM and EZ integrity throughout, whereas macula-off patients had ELM and EZ integrity restored in 89.7% and 86.2% cases, respectively, with a resultant increase in final BCVA. Significant associations were found between preoperative macular involvement and ELM/EZ restoration. ELM/EZ recovery was also inversely associated with CME development. Significant associations were also found between final BCVA and preoperative BCVA and EZ recovery. CME and SB development were equally distributed between the 2 groups. CONCLUSION: Prompt surgery for macula-off RRD allows the progressive recovery of outer retinal layers and significant visual gain.

Effect of Dexamethasone Intravitreal Implant on Visual Acuity and Foveal Photoreceptor Integrity in Macular Edema Secondary to Retinal Vascular Disease.

PURPOSE: The aim of this study was to evaluate the effect of the dexamethasone intravitreal (DEX) implant on the external limiting membrane (ELM) and ellipsoid zone (EZ) integrity in treatment-naïve patients with macular edema (ME) secondary to retinal vascular disease (RVD). METHODS: This is a retrospective study conducted on patients with ME secondary to RVD, who underwent a DEX implant. RESULTS: One-hundred eyes were included. Mean age was 70.3 ± 11.1 years. Mean ELM integrity significantly improved from 1,575.9 ± 285.9 µm at baseline to 1,711.7 ± 244.0 µm at month 3 (p < 0.0001). Similarly, there was a significant improvement in EZ integrity from baseline to month 3 (1,531.5 ± 317.1 vs. 1,694.3 ± 252.8 µm, respectively, p < 0.0001). At month 3, mean visual acuity (VA) gain was 9.9 ± 14.1 letters (p < 0.0001). Mean central retinal thickness (CRT) significantly decreased by -193.2 ± 185.7 µm from baseline to month 3 (p < 0.0001). Mean changes in VA and CRT were significantly correlated with baseline ELM integrity (p = 0.0065 and p = 0.0046, respectively) and EZ integrity (p = 0.0300 and p = 0.0035, respectively). At month 3, the proportion of eyes which had an intact ELM (mean difference 16.0%, 95% CI 5.4-26.4%, p = 0.0033) and EZ (mean difference 12.0%, 95% CI 1.8-22.1%, p = 0.0210) was significantly higher than at baseline. CONCLUSIONS: DEX implant was able to significantly improve ELM and EZ integrity in naïve patients with ME.

Optical Coherence Tomography based indices in predicting functional outcome of macular hole surgery: A retrospective chart review.

OBJECTIVES: The objective of this study was to assess the utility of novel macular hole indices of Optical Coherence Tomography (OCT) and predicting the functional outcome of surgery. METHODS: This was a retrospective chart review of 28 eyes who underwent surgery for idiopathic Full Thickness Macular Hole (FTMH) at The Aga Khan University Hospital (AKUH), Karachi from January 2016 to March 2020. Data of preoperative OCTs were recovered from data server of OCT machine. Measurements of the pre-operative OCTs were calculated using caliper function of OCT software by two independent technicians. Parameters included Macular Hole Index (MHI), Traction Hole Index (THI), Hole Form Factor (HFF) and Diameter Hole Index (DHI) were recorded. Receiver operating characteristic (ROC) curve was used to evaluate the performance of DHI, THI, HFF and MHI for improved BCVA after surgery, by looking at sensitivity, specificity and area under curve (AUC). P-value of <0.05 was considered significant. RESULTS: Out of 30 eyes, final data analysis was done for 28 eyes. Mean age was 61.5 ± 6.2 years. Mean pre-operative and 6 months post-operative LogMAR best corrected visual acuity (BCVA) was 0.84 ± 0.23 and 0.32 ± 0.30 (p-value <0.001). Area under the curve with 95% confidence interval estimated for DHI, THI, HFF, and MHI was [0.750 (0.559 to 0.889)], [0.827 (0.637 to 0.943)], [0.846 (0.660 to 0.954)], [0.827 (0.637 to 0.943)]. Cut off values for predicting good functional outcome (post-op BCVA equal or better that 0.4) for DHI, THI, HFF and MHI were 0.454, 1.086, 0.856 and 0.501 respectively. All ROC value of less than 0.5 were considered unlikely to predict functional outcomes with macular hole indices. CONCLUSION: Novel macular hole indices can be used as a tool to predict the functional outcomes of macular hole surgery. Larger studies may be required to assess their wider effectiveness.

External limiting membrane angle as a composite predictive index for post-operative ELM closure in full thickness macular holes.

AIM: To evaluate pre-operative qualitative and quantitative parameters of external limiting membranes (ELM) and other associated full thickness macular holes (FTMH) features and their predictive values for post-operative anatomical and functional outcomes. METHODS: This was a retrospective study of 48 eyes that underwent vitrectomy with internal limiting membrane (ILM) peeling for FTMH and had type 1 closure. All subjects underwent optical coherence tomography (SDOCT, Heidelberg, Spectralis), and the eyes were divided into complete ELM closure (CEC) and incomplete ELM closure (IEC) groups based on the post-operative OCTs within 2 months, and ROC curves were used to estimate which of the pre-operative parameters could best predict eyes falling in the CEC group. RESULTS: The mean pre-op ELM defect was smaller in CEC group (594 µm vs 1126 µm, p < 0.001) and so was the pre-op EZ defect (770 µm vs 1186 µm, p = 0.001). The mean ELM angle also was smaller in the CEC group (51.6° vs 102.5°, p < 0.001) and so was the mean hole inlet distance (353 µm vs 596 µm, p < 0.001). The post-operative ELM defect showed a significant negative correlation with visual acuity (r = - 0.319; p = 0.027). The ELM angle was most predictive with an AUROC of 0.958, and a cut-off of 68.3° had a sensitivity of 90% and a specificity of 89%. CONCLUSION: Our study introduces a novel parameter called the ELM angle and proves that it has a high sensitivity and specificity in predicting complete ELM reformation post-surgery in the short term as well as the long term.

The prognostic value of total macular external limiting membrane and ellipsoid zone damage for clinical outcome in treatment-resistant neovascular age-related macular degeneration.

PURPOSE: To examine the prognostic value of the extent of damage to the ellipsoid zone (EZ) and external limiting membrane (ELM) in response to the treatment of age-related macular degeneration (AMD) eyes switched from ranibizumab to aflibercept. METHODS: This is a retrospective study of patients with neovascular AMD resistant to ranibizumab defined as having persistent intra- or subretinal fluid on OCT scans despite at least 6-month treatment and switched to aflibercept. Clinical data was collected and quantitative measurements of the area of EZ and ELM damage were obtained, on en-face optical coherence tomography images, at the time of switch to aflibercept (baseline) and up to 6 months of follow-up. RESULTS: The study included 71 eyes (52.1% right eye) of 71 patients. At baseline, there was a correlation between the size of the EZ and ELM damaged area and BCVA (R = -0.39, p = 0.001 and R = -0.47, p < 0.001, respectively). The EZ and ELM damaged areas maintained correlation with BCVA at 6 months (R = -0.28, p = 0.01 and R = -0.39, p = 0.001, respectively). Central retinal thickness did not correlate with BCVA at the time of switch (p = 0.38) or at 6 months (p = 0.36). CONCLUSIONS: The extent of damage to the EZ and ELM correlates with BCVA following a switch in treatment.

Effects of inverted internal limiting membrane technique and insertion technique on outer retinal restoration associated with glial proliferation in large macular holes.

PURPOSE: To compare the effects of inverted internal limiting membrane (ILM) flap technique and ILM insertion technique for large macular hole (MH) on glial proliferation, retinal outer layer restoration, and visual function. METHODS: This retrospective, observational study included 25 eyes with large MH (minimum diameter, ≥ 400 µm) treated using the inverted ILM flap or insertion technique. The inverted flap group was defined as flipping the ILM upside down on the MH (13 eyes) and the insertion group as inserting multiple ILM layers into the MH (12 eyes). RESULTS: Glial proliferation in the photoreceptor layer at 1 month and the final visit was significantly less frequent in the inverted flap group than in the insertion group (61.5% vs. 100%, p = 0.039; 23.1% vs. 100%, p = 0.001). The mean postoperative external limiting membrane defect was 140.4 ± 286.2 µm in the inverted flap group, significantly narrower than that in the insertion group (364.6 ± 181.6 µm; p = 0.016). The mean postoperative ellipsoid zone defect was 235.3 ± 214.2 µm in the inverted flap group, which was almost significantly narrower than that in the insertion group (496.3 ± 445.6 µm; p = 0.068). The change in the best-corrected visual acuity was significantly better in the inverted flap group than that in the insertion group (+ 18.5 vs. + 9.0 letters). CONCLUSION: Compared with patients treated with the insertion technique, those treated with the inverted ILM flap technique had significantly less glial proliferation at the photoreceptor space, more preferable outer retinal formation, and better visual improvement.

Association of retinal biomarkers and choroidal vascularity index on optical coherence tomography using binarization method in retinitis pigmentosa.

PURPOSE: To investigate the association of retinal biomarkers with the choroidal parameters in retinitis pigmentosa (RP). METHODS: This prospective study included 69 eyes of 36 patients with RP. Choroidal vascularity index (CVI) was defined as the ratio of luminal area to stromal area after binarization on EDI-OCT images. Choroidal thickness (CT); peripapillary CT, the disruptions of the ellipsoid zone (EZ) and external limiting membrane (ELM); and the existence of disorganization of the retinal inner layers (DRIL) and epiretinal membrane (ERM) in central 1000 µm were noted. RESULTS: Having DRIL and the disruption of EZ and ELM was significantly associated with higher CVI (p < 0.001, p = 0.001, and p = 0.002 respectively) and lower peripapillary CT in temporal sector (p = 0.031, p = 0.012, and p = 0.043 respectively). Having ERM, the disruption of EZ and ELM was significantly associated with lower visual acuity (VA) (p = 0.044, p < 0.001, and p < 0.001 respectively). The eyes with ERM had significantly lower peripapillary retinal nerve fiber thickness (pRNFLT) (p = 0.040). The mean peripapillary CT significantly and positively correlated with the temporal, nasal, superonasal, and the mean pRNFLT (r = 0.258, p = 0.036, r = 0.252, p = 0.041, r = 0.260, p = 0.035, r = 0.280, p = 0.023 respectively). VA did not significantly correlate with CT, peripapillary CT, or CVI (p > 0.05). CONCLUSION: The disruption outer retinal segment integrity was significantly associated with higher CVI and lower peripapillary CT in temporal segment. ERM and disruption of ELM and EZ were associated with worse VA. VA did not significantly correlate with CT, peripapillary CT, or CVI.

Outer retinal layers as predictors of visual acuity in retinitis pigmentosa: a cross-sectional study.

PURPOSE: To evaluate the integrity of the outer retinal layers-outer nuclear layer (ONL), external limiting membrane (ELM), ellipsoid (EZ), and interdigitation band (IZ)-using spectral-domain optical coherence tomography and estimate their effect on visual acuity in retinitis pigmentosa (RP). METHODS: A cross-sectional study was performed in the Ophthalmology Department of Hospital de Braga, Portugal. Patients with RP followed in the Hospital de Braga during January to August 2017 were included. Exclusion criteria were lack of data, macular edema due to RP, and concomitant retinal, optic nerve, or corneal disease that could interfere with visual acuity. Age, sex, time from diagnosis, phakic status, ONL thickness, and presence or absence of foveal ELM, EZ, and IZ were correlated to the best-corrected visual acuity (BCVA). RESULTS: Forty-eight eyes were analyzed. There was a strong and positive correlation in BCVA between both eyes (p < .001*). ONL thickness was decreased in 95.8%. The EZ was the most absent layer (79.2%), followed by IZ (70.8%) and ELM (45.8%). A positive family history (p = .04*) and increased time from diagnosis (p = .037*) correlated with worse BCVA. A thicker ONL (p = .001*) and the presence of subfoveal ELM (p < .001*), EZ (p < .001*), and IZ (p = .02*) are correlated with better BCVA. There was a strong and positive correlation between the number of layers affected and a lower BCVA (p < .001). The presence of EZ was a significant predictor of BCVA (p = .02*). CONCLUSIONS: The status of the outer retinal layers seems to influence BCVA. The status of the EZ was the most important predictor of BCVA but the ONL, ELM, and IZ may have a cumulative effect in the progression of visual loss.

Evaluation of the correlation between quantitative measurement of the foveal avascular zone and retinal vessel density and outer retinal disruptions in diabetic patients

Background/aim: The aim of the current study was to evaluate the correlation between the integrity of the outer retinal layers on optical coherence tomography (OCT) and objective parameters of retinal microvascular perfusion on optical coherence tomography angiography (OCTA). Materials and methods: A total of 105 eyes of 54 diabetic patients were included in the study. Integrity of the outer retinal layers including the external limiting membrane (ELM), ellipsoid zone (EZ), and interdigitation zone (IZ) was assessed by spectral-domain optical coherence tomography. The foveal avascular zone (FAZ) area and vessel density (VD) measurements in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) in all the Early Treatment Diabetic Retinopathy Study (ETDRS) sectors were evaluated by OCTA. Associations between the quantitative measurement of the FAZ and retinal VD measurements and outer retinal disruptions were evaluated. Results: The FAZ area was correlated with outer retinal layer disruption both in the superficial plexus (r = 0.244, 0.228, 0.212, P = 0.013, 0.02, 0.031 for the ELM, EZ, and IZ, respectively) and the deep capillary plexus (r = 0.298, 0.234, 0.197, P = 0.002, 0.019, 0.048 for the ELM, EZ, and IZ, respectively). A significant relationship was also found between the VD measurements in the SCP and DCP in ETDRS sectors and the outer retinal layers disruption. Conclusion: The results of the current study show a significant relationship between the quantitative OCTA parameters and the integrity of the outer retinal layers. This finding reveals a correlation between retinal capillary nonperfusion and outer retinal disruption in eyes with diabetic retinopathy.

Retinal pigmental epithelium elevation and external limiting membrane interruption in myopic choroidal neovascularization: correlation with activity.

PURPOSE: To describe the morphological changes in myopic choroidal neovascularization (mCNV) on spectrum domain optical coherence tomography (SD-OCT) and to find a new strategy to evaluate their activity. METHODS: Characteristics of SD-OCT and fundus fluorescein angiography (FFA) before and after ranibizumab treatment of 52 eyes with active mCNV were analyzed. SD-OCT parameters associated with mCNV activity and the clinical significance of their sensitivity and specificity were analyzed using FFA as a standard reference. Retinal pigment epithelium (RPE) elevation was noted as highly correlated to the mCNV activity. RESULTS: Intraobserver agreement was substantial for all OCT parameters. However, interobserver agreement was low for intraretinal fluid (IRF). To evaluate the CNV activity, sensitivity of presence of subretinal fluid (SRF) and interruption of ellipsoid zone (EZ) was 23.9 and 82.1%, and specificity was 97.5 and 19.8%. External limiting membrane (ELM) interruption showed high sensitivity (97.0%) but low specificity (55.6%) due to the development of RPE elevation. A novel two-step procedure using ELM interruption and RPE elevation was developed to evaluate mCNV activity with sensitivity 92.5% and specificity 95.1%, respectively. Final agreement was as high as 93.9%, with a kappa value of 0.877 (P < 0.001). CONCLUSIONS: A novel two-step diagnostic procedure combining ELM interruption with RPE elevation is considered a valuable guide for diagnosis and monitoring of mCNV.

Multifocal electroretinography changes at the 1-year follow-up in a cohort of diabetic macular edema patients treated with ranibizumab.

PURPOSE: To determine the changes in the multifocal electroretinogram (mfERG) at 1 year in a clinical series of diabetic macular edema (DME) patients treated with ranibizumab (RNBZ) using a pro re nata protocol. METHODS: We analyzed a clinical series of 35 eyes of 35 patients with DME at baseline and after treating them with RNBZ over 1 year, in order to determine the change in the macular function, which was assessed by means of the response density and the implicit time of the first-order kernel (FOK) P1 wave of the mfERG at the foveola (R1), fovea (R2) and parafovea (R3). These electrophysiological parameters were studied taking into account different independent variables, such as DME type, degree of diabetic retinopathy (DR), level of preservation of both the ellipsoid zone (IS/OS) and the external limiting membrane (ELM) and changes in central retinal thickness (CRT) and total macular volume (TMV). We also studied the relationship between the response density and the best-corrected visual acuity (BCVA). RESULTS: Eyes with cystic and spongiform DME showed better response density with respect to the serous type (p < 0.001) at baseline. Similarly, eyes with high IS/OS and ELM preservation rates showed higher initial response density compared to the others (p < 0.001). Eyes with moderate DR had better response density compared to those with severe and proliferative DR (p = 0.001). At the beginning of the study, those eyes with proliferative and severe DR showed longer implicit times with respect to those with moderate DR (p = 0.04). The response density significantly increased in eyes that anatomically restored the IS/OS and the ELM after being treated with RNBZ (both p < 0.001). Similarly, eyes with spongiform DME further improved the response density with respect to those with cystic and serous DME (p < 0.001). On the contrary, eyes with hard exudates showed less improvement in their response density at the end of the study (p < 0.001). We observed a significant relationship between BCVA and the response density achieved at the end of the study (p = 0.012). Eyes with severe and proliferative DR significantly shortened implicit time compared to those with moderate DR (p = 0.04). CONCLUSIONS: The multifocal electroretinogram allowed us to differentiate groups of eyes with DME according to their electrophysiological profile, both initially and after being treated with RNBZ. Ranibizumab increased the response density in all DME types included in the study, with a maximum response in those eyes with spongiform type. Once treated with RNBZ, the macular electrophysiological activity improved in eyes that had a well-preserved ellipsoid zone and ELM. The presence of hard exudates was a limitation to the response density achieved at the foveola.

Quantitative analysis of external limiting membrane, ellipsoid zone and interdigitation zone defects in patients with macular holes.

PURPOSE: To investigate the correlation between the length of external limiting membrane (ELM), ellipsoid zone (EZ) and interdigitation zone (IZ) defects and visual prognosis in patients undergoing macular hole (MH) surgery, using spectral-domain optical coherence tomography (SD-OCT). METHODS: This is a retrospective, consecutive, observational case series study. Fifty-two eyes of 52 patients with primary MH were evaluated. A quantitative analysis of ELM, EZ and IZ defects was performed preoperatively and at 3 and 6 months postoperatively using SD-OCT. The correlation between pre- and postoperative ELM, EZ and IZ defects and the best-corrected visual acuity (BCVA) was investigated. RESULTS: The lengths of ELM, EZ and IZ defects correlated significantly with BCVA in each study period (P < 0.001). Preoperative measures of these band defects were also associated with visual outcomes 3 and 6 months after surgery (P < 0.05). Considering all preoperative parameters, the length of the ELM defect was the factor most strongly correlated with BCVA at 6 months (ß = 0.643, P < 0.012). The integrity of the ELM was the only factor significantly associated with BCVA at 6 months (ß = 0.427; P = 0.004). CONCLUSIONS: The preoperative length of the ELM defect is the strongest predictor of visual acuity after MH surgery. Postoperative integrity of the ELM is significantly associated with visual restoration after surgical treatment of MH.