Temporal variation of optical coherence tomography biomarkers as predictors of anti-VEGF treatment outcomes in diabetic macular edema.

PURPOSE: To report a longitudinal analysis of specific optical coherence tomography (OCT) features in eyes with diabetic macular edema (DME) treated with anti-VEGF. METHODS: A total of 133 eyes of 103 consecutive patients with center-involving DME were included in the study. The eyes were treated between August 2008 and April 2019 with three monthly intravitreal anti-VEGF injections, either with or without prompt or deferred laser, followed by pro re nata (PRN) re-treatment. The following OCT biomarkers were evaluated: subfoveal neuroretinal detachment (SND) (defined as present (SND+) or absent (SND-)), hyperreflective retinal foci (HRF) number (defined as: absent/few(HRF-) or moderate/many (HRF+)), external limiting membrane (ELM) integrity, central macular thickness (CMT), and central retinal thickness (CRT). Changes in SND status and in the number of HRF were evaluated at each DME recurrence throughout the follow-up(FU) period. Mutual correlation among OCT biomarkers and their relationship with visual and anatomic outcomes were assessed both at baseline and over the FU period. RESULTS: The mean FU was 71.2 months (SD 28.4; min. 12-max. 111). At baseline, the prevalence of SRD+ was 27.8% and a high number of HRF were detected in 41.4% of the eyes. A significant reduction in the number of HRF, CMT, CRT, and in the prevalence of SND was recorded in the post-loading phase (p-value <0.0001). In DME recurrences, the presence of SND+ and HRF+ was significantly more frequent in eyes with baseline SND+ and HRF+ compared to eyes presenting baseline SND- and HRF- (p-value <0.0001). No role of SND (p-value: 0.926) and HRF (p-value: 0.281) as baseline predictors of visual and anatomic outcomes was demonstrated, while a worse visual outcome was significantly correlated with a higher incidence of relapsing SND+ (p-value <0.0001) and HRF+ (p-value <0.0028) throughout the FU period. CONCLUSION: In this study, SND and HRF were frequently present in DME recurrences with the same pattern exhibited at baseline, suggesting that these OCT biomarkers may characterize a specific pattern of DME that repeats over time. Moreover, the results suggested that the persistence and recurrence of SND and HRF may account for a decrease in visual function more than the baseline prevalence of these biomarkers. Further studies are required to confirm these findings.

Intravitreal Recombinant Tissue Plasminogen Activator and Sulphur Hexafluoride Gas for Submacular Haemorrhage Displacement in Age-Related Macular Degeneration: Looking behind the Blood.

PURPOSE: To evaluate the effectiveness of recombinant tissue plasminogen activator (rtPA) and sulphur hexafluoride gas (SF6) intravitreal injection for the displacement of large submacular haemorrhages (SMH) secondary to neovascular age-related macular degeneration and for guiding the selection of additional treatments or observations for choroidal neovascularization (CNV). METHODS: The medical records of consecutive patients with recent-onset, large SMH, treated at Sacro Cuore Hospital from January 2004 to May 2016, were retrospectively analysed. All eyes underwent a 0.05-mL intravitreal injection of 50 µg rtPA, 0.3 mL of 100% SF6, and then face-down positioning. Afterwards, the eyes received additional treatments for CNV or observation, based on the severity and extent of the underlying pathology. The multimodal imaging features revealed after blood displacement were analysed and then correlated to the treatment selected as a second therapeutic option. RESULTS: A total of 96 eyes met the inclusion criteria and was evaluated in this study. SMH was displaced from the fovea in the majority of the eyes (76%), allowing several diagnostic tools to evaluate the underlying macular features. In 19 cases (19.8%) exhibiting severe macular damage, no additional treatment was applied. In the remaining eyes, subsequent treatments included anti-vascular endothelial growth factor injections (44.8%), photodynamic therapy (n = 2), and submacular surgery (35.4%). Statistically significant correlations were found between the macular findings revealed after blood displacement and the additional treatments or observations selected for the underlying disease. The mean follow-up was 35 months. Improvements in visual acuity were statistically significant up to 3 years. CONCLUSION: Intravitreal rtPA and gas injection was found to be effective for the displacement of large SMH, allowing postoperative diagnostic testing, and thus guiding the opportunity to apply further treatments. The addition of subsequent individualized treatments may allow long-term visual gain in selected cases.

New Insights Into the Development and Progression of Geographic Atrophy After Full Thickness Autologous Choroidal Graft.

Purpose: To investigate if the contiguity between native and transplanted retinal pigment epithelium (RPE) represents a protective factor against the progression of atrophy after autologous choroidal graft. In addition, the changes in fundus autofluorescence (FAF) in the contiguous and noncontiguous RPE areas were explored. Methods: The first postoperative reliable FAF image was selected and divided into sectors based on the characteristics of the RPE at the edge of the graft. The sectors were categorized into three groups: contiguous RPE, noncontiguous RPE, and not classifiable. The area of RPE atrophy, inside and outside the graft, was measured for each sector at baseline, one, three, and five years of follow-up. The FAF pattern outside the graft was evaluated for every sector at baseline and during the follow-up. Results: Nineteen patients met the inclusion criteria and were included in this study. Trend analysis showed that the atrophy progression outside the graft was statistically significant in areas where native and transplanted RPE were noncontiguous (P < 0.0001) yet not so in contiguous areas (P < 0.058). Inside the graft, both groups showed an increase in atrophy over time. In addition, the noncontiguous group developed more severe increased FAF patterns compared with the contiguous group. Conclusions: RPE contiguity after autologous choroidal graft seems to be a protective factor against atrophy progression, whereas any area of damaged or absent RPE tends to enlarge over time. This may suggest that the transplantation of an RPE sheet is more likely to be effective than an RPE cell suspension.

Anti-Vascular Endothelial Growth Factor Treatment for Diabetic Macular Edema in a Real-World Clinical Setting.

PURPOSE: To report the long-term outcomes of intravitreal anti-vascular endothelial growth factor (VEGF) treatment for diabetic macular edema (DME) in a real-world clinical setting and to assess the efficacy of subsequent alternative treatments in eyes with suboptimal response to anti-VEGF. DESIGN: Retrospective interventional case series. METHODS: The medical records of consecutive eyes with center-involving DME, treated between August 2008 and June 2015 with 3 monthly intravitreal anti-VEGF injections-with or without prompt or deferred laser-followed by pro re nata re-treatment, were reviewed. A subgroup of eyes that were unresponsive to the treatment received subsequent alternative therapeutic options, including switching to another anti-VEGF drug, intravitreal injection of dexamethasone, and vitrectomy. RESULTS: A total of 170 eyes of 129 patients were included in the study. The mean follow-up (FU) was 45.6 months (SD 18; minimum 12-maximum 81). The change in mean best-corrected visual acuity (BCVA) at 1-year FU was +5 ETDRS letters (P < .0001). Improvement in BCVA was statistically significant up to 5 years. Improvement in central macular thickness (CMT) was statistically significant up to the last FU visit. In eyes with suboptimal response, no significant visual improvement was found by switching to another anti-VEGF (P =.4347). Twenty-four eyes treated with intravitreal dexamethasone and 14 with vitrectomy exhibited a significant reduction in CMT with variable functional responses. In these eyes, better BCVA gain was found in cases with an early change of the treatment strategy. CONCLUSION: The results support treatment with intravitreal anti-VEGF for DME in real-world clinical settings and suggest that an early change of the therapeutic strategy should be considered for eyes unresponsive to the treatment.

INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE VERSUS COMPLETE INTERNAL LIMITING MEMBRANE REMOVAL IN MYOPIC MACULAR HOLE SURGERY: A Comparative Study.

PURPOSE: To compare the results of vitrectomy with complete internal limiting membrane (ILM) removal and inverted ILM flap in the treatment of myopic macular hole (MMH). METHODS: Seventy eyes of 68 patients with MMH undergone pars-plana vitrectomy (PPV) with either complete ILM removal (n = 36, Group 1) or inverted ILM flap technique (n = 34, Group 2) were included in the study. Outcomes measured were the rate of MMH closure assessed by optical coherence tomography (OCT) and visual acuity (BCVA) at six months. RESULTS: Closure of MMH was achieved in 22 cases of Group 1 (61%) and in 32 cases of Group 2 (94%). Surgical failure was reported in 14 cases of Group 1 (39%) and in one case of Group 2 (3%). Average best-corrected visual acuity (BCVA) changed from 0.60 to 0.58 in Group 1 (P = 0.329) and from 0.70 to 0.39 in Group 2 (P < 0.01). Logistic regression analysis showed that inverted ILM flap technique was associated with 22 times higher probability of anatomic success, regardless of the MMH diameter. CONCLUSION: Inverted ILM flap should be preferred to complete ILM removal for the treatment of MMH. The outcomes reported with this technique were better than any other technique described until now.

Cystoid macular edema after pars plana vitrectomy for idiopathic epiretinal membrane.

BACKGROUND: To evaluate the incidence of cystoid macular edema (CME) after 23-gauge pars plana vitrectomy (PPV) with or without combined cataract surgery for the treatment of idiopathic epiretinal membrane (ERM). METHODS: Retrospective, non-comparative, interventional case series. Data included patient age, indication for surgery, and intra- and post-operative complications. The follow-up lasted 1 year. Best-corrected visual acuity (BCVA logMAR), central foveal thickness (CFT micron-µ) and the incidence of intra-retinal cysts were evaluated. CME was defined as post-operative observation of intra-retinal cysts at optical coherence tomography, preventing improvement or causing reduction of BCVA when compared to the pre-operative value. Statistical analysis was performed to identify the risk factors of CME. RESULTS: Two hundred and forty two eyes of 242 patients underwent PPV for the treatment of idiopathic ERM. Statistical analysis showed that the presence of preoperative intra-retinal cysts were associated with persistent CME following surgery (odds ratio 3.89; 95%CI: 1.63-9.28, P = 0.0004). However, postoperative CME occurred in 10 % of eyes that did not show preoperative CME. In addition, there was a significant correlation between the baseline value of CFT and the values of CFT at each time point during the follow up (p < 0.0001), with greater values of the pre-operative thickness correlating to greater values of post-operative thickness. CONCLUSIONS: Persistent or new CME following surgery for idiopathic ERM are frequently identified after PPV for ERM. The statistical results of the current study suggest that intraretinal cysts and increased preoperative CFT are associated with reduced visual acuity after surgery.

Quality of Vision Index: a new method to appraise visual function changes in age-related macular degeneration.

PURPOSE: To explore the correlation between psychophysical measures of visual function and vision-related quality of life (QOL) in exudative age-related macular degeneration (AMD) and to obtain a new quality of vision index expressed as corrected visual acuity (cVA) that is scaled like visual acuity (VA), but that incorporates the weighted contribution of VA, contrast sensitivity (CS), and reading ability. METHODS: Visual acuity, CS, and reading ability were measured in 293 patients with AMD in this multicenter prospective study. Vision-related QOL was quantified by the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25). The validity of the questionnaire was assessed using Rasch analysis. The relationship between psychophysical tests and NEI-VFQ-25 scores was investigated. A cVA index was developed integrating Rasch-scaled NEI-VFQ-25 score with VA, CS, and reading ability as a tool to be used for evaluating vision-related QOL on the same scale as VA. RESULTS: A total of 27.5% of the variability of VFQ score was found to be explained by VA alone in patients with AMD. The proportion of Rasch-scaled QOL estimate variance explained by cVA was 33.2% as compared to 27.5% explained by VA and 24.5% by CS, which was a statistically significant improvement in both cases (p=0.015 and p<0.001, respectively). The correlation of reading ability with vision-related QOL was largely mediated by VA and CS and therefore it was not retained in the vision index. CONCLUSIONS: Visual acuity is poorly correlated with vision-related QOL in patients with AMD. Even though the new cVA index is a new method which better correlates with vision-related QOL, the major components of the individual perception of vision remain unexplained by common psychometric tests.

Profile of lipid and protein autacoids in diabetic vitreous correlates with the progression of diabetic retinopathy.

OBJECTIVE: This study was aimed at obtaining a profile of lipids and proteins with a paracrine function in normal and diabetic vitreous and exploring whether the profile correlates with retinal pathology. RESEARCH DESIGN AND METHODS: Vitreous was recovered from 47 individuals undergoing vitreoretinal surgery: 16 had nonproliferative diabetic retinopathy (NPDR), 15 had proliferative diabetic retinopathy, 7 had retinal detachments, and 9 had epiretinal membranes. Protein and lipid autacoid profiles were determined by protein arrays and mass spectrometry-based lipidomics. RESULTS: Vitreous lipids included lipoxygenase (LO)- and cytochrome P450 epoxygenase (CYP)-derived eicosanoids. The most prominent LO-derived eicosanoid was 5-hydroxyeicosate traenoic acid (HETE), which demonstrated a diabetes-specific increase (P = 0.027) with the highest increase in NPDR vitreous. Vitreous also contained CYP-derived epoxyeicosatrienoic acids; their levels were higher in nondiabetic than diabetic vitreous (P < 0.05). Among inflammatory, angiogenic, and angiostatic cytokines and chemokines, only vascular endothelial growth factor (VEGF) showed a significant diabetes-specific profile (P < 0.05), although a similar trend was noted for tumor necrosis factor (TNF)-alpha. Soluble VEGF receptors R1 and R2 were detected in all samples with lowest VEGF-R2 levels (P < 0.05) and higher ratio of VEGF to its receptors in NPDR and PDR vitreous. CONCLUSIONS: This study is the first to demonstrate diabetes-specific changes in vitreous lipid autacoids including arachidonate and docosahexanoate-derived metabolites indicating an increase in inflammatory versus anti-inflammatory lipid mediators that correlated with increased levels of inflammatory and angiogenic proteins, further supporting the notion that inflammation plays a role the pathogenesis of this disease.

Postoperative complications and intraocular pressure in 943 consecutive cases of 23-gauge transconjunctival pars plana vitrectomy with 1-year follow-up.

BACKGROUND: To report the rate of postoperative complications in 943 consecutive eyes operated on with 23-gauge transconjunctival pars plana vitrectomy. METHODS: Single-center, retrospective, noncomparative, interventional case series. Nine hundred and forty-three eyes underwent 23-gauge transconjunctival core and peripheral vitrectomy with peripheral laser at the sclerotomy sites from May 2005 through April 2008. The main outcome measures were intraocular pressure at 1 day and at 1 week and intra- and postoperative complications with at least 6-month follow-up. RESULTS: Eight hundred and thirty-one eyes (88%) did not have either significant intra- or postoperative complications. Sclerotomy leakage requiring suture occurred in 37 eyes (3.9%). One choroidal detachment (0.1%) spontaneously resolved 1 week after surgery. At postoperative Day 1, 31 eyes (3.3%) experienced transient hypotony. Forty-five eyes (4.8%) presented a subtle vitreous hemorrhage that resolved spontaneously. Two retinal detachments (0.2%) occurred, one at 1 month and one at 3 months. They resolved with one further vitrectomy. Seven hundred and forty eyes completed the 12-month follow-up and presented no further complications. CONCLUSION: Twenty-three-gauge complete vitrectomy and peripheral laser seem safe for a variety of vitreoretinal surgical procedures. The rate of post- and intraoperative complications compares favorably with 25-gauge and with the standard 20-gauge vitrectomy.

Combination of photodynamic therapy and intraocular triamcinolone for exudative age-related macular degeneration and long-term chorioretinal macular atrophy.

OBJECTIVE: To evaluate the long-term effect of intravitreal triamcinolone acetonide (IVT) treatment combined with photodynamic therapy (PDT) vs PDT alone for neovascular age-related macular degeneration. METHODS: Prospective randomized study. Eighty-four patients were enrolled to receive PDT (n = 41) or IVT treatment followed by PDT (n = 43) within approximately a 7- to 15-day interval. All patients were naive to treatment. At baseline and each follow-up visit at 3, 6, 12, and 24 months, measurement of best-corrected visual acuity (VA), fluorescein angiography, indocyanine green angiography, and optical coherence tomography were performed. Mean changes in VA and retreatment rate were considered as primary outcome indicators. Analysis of vascular choroidal changes documented by indocyanine green angiography and fundus autofluorescence measurements were also performed. RESULTS: Mean VA increased at 1 month of follow-up but decreased progressively by the 24-month point in both groups (P = .74). The retreatment rate was significantly lower (P < .001) in the combined therapy group. Choroidal hypoperfusion/nonperfusion (P < .001) and areas with decreased/absent fundus autofluorescence within the PDT spot area were significantly greater with combined therapy (P < .001). CONCLUSIONS: Combination IVT treatment with PDT seemed to be more effective for managing neovascular age-related macular degeneration, but long-term analysis failed to demonstrate functional benefits.

Photodynamic therapy increases the eligibility for feeder vessel treatment of choroidal neovascularization caused by age-related macular degeneration.

PURPOSE: To report angiographic observations about feeder vessel identification after photodynamic therapy in patients with choroidal neovascularization caused by age-related macular degeneration. DESIGN: Cohort study. METHODS: We analyzed fluorescein and indocyanine green dynamic angiography in 156 eyes of 145 patients before and after photodynamic therapy to identify the feeder vessels of the choroidal neovascular membrane. RESULTS: Before photodynamic therapy one or more feeder vessel could be detected in 35 (22.4%) out of 156 eyes with choroidal neovascularization. Three months after photodynamic therapy, a feeder vessel could be identified in 112 (84.2%) out of 133 eyes with persistent choroidal neovascularization. Among these, 16 eyes received direct laser photocoagulation of the feeder vessel and did not need any further photodynamic therapy. CONCLUSION: Previous photodynamic therapy improves the detection of the feeder vessel of the choroidal neovascularization. A sequential combined therapy (photodynamic and feeder vessel treatment) could be considered as an alternative to multiple photodynamic treatments.