Retrospective validation of the postnatal Growth and Retinopathy of Prematurity (G-ROP) criteria in a Swiss cohort.

BACKGROUND: Currently used screening criteria for retinopathy of prematurity (ROP) show high sensitivity for predicting treatment-requiring ROP but low specificity; over 90% of examined infants do not develop ROP that requires treatment (type 1 ROP). A novel weight gain-based prediction model was developed by the G-ROP study group to increase the specificity of the screening criteria and keep the number of ophthalmic examinations as low as possible. This retrospective cohort study aimed to externally validate the G-ROP screening criteria in a Swiss cohort. METHODS: Data from 645 preterm infants in ROP screening at Inselspital Bern between January 2015 and December 2019 were retrospectively retrieved from the screening log and analysed. The G-ROP screening criteria, consisting of 6 trigger parameters, were applied in infants with complete data. To determine the performance of the G-ROP prediction model for treatment-requiring ROP, sensitivity and specificity were calculated. RESULTS: Complete data were available for 322 infants who were included in the analysis. None of the excluded infants had developed type 1 ROP. By applying the 6 criteria in the G-ROP model, 214 infants were flagged to undergo screening: among these, 14 developed type 1 ROP, 9 developed type 2 ROP, and 43 developed milder stages of ROP. The sensitivity for predicting treatment-requiring ROP was 100% (CI, 0.79-1.00), and the specificity was 41% (CI, 0.35 -0.47). Implementing the novel G-ROP screening criteria would reduce the number of infants entering ROP screening by approximately one third. CONCLUSIONS: The overall prevalence of treatment-requiring ROP was low (2.15%). Previously published performance parameters for the G-ROP algorithm were reproducible in this Swiss cohort. Importantly, all treatment-requiring infants were correctly identified. By using these novel criteria, the burden of screening examinations could be significantly reduced.

Effect of Inhibition of Colony-Stimulating Factor 1 Receptor on Choroidal Neovascularization in Mice.

Neovascular age-related macular degeneration is one of the leading causes of blindness. Microglia and macrophages play a critical role in choroidal neovascularization (CNV) and may, therefore, be potential targets to modulate the disease course. This study evaluated the effect of the colony-stimulating factor-1 receptor inhibitor PLX5622 on experimental laser-induced CNV. A 98% reduction of retinal microglia cells was observed in the retina 1 week after initiation of PLX5622 treatment, preventing accumulation of macrophages within the laser site and leading to a reduction of leukocytes within the choroid after CNV induction. Mice treated with PLX5622 had a significantly faster decrease of the CNV lesion size, as revealed by in vivo imaging and immunohistochemistry from day 3 to day 14 compared with untreated mice. Several inflammatory modulators, such as chemokine (C-C motif) ligand 9, granulocyte-macrophage colony-stimulating factor, soluble tumor necrosis factor receptor-I, IL-1α, and matrix metallopeptidase-2, were elevated in the acute phase of the disease when microglia were ablated with PLX5622, whereas other cytokines (eg, interferon-γ, IL-4, and IL-10) were reduced. Our results suggest that colony-stimulating factor-1 receptor inhibition may be a novel therapeutic target in patients with neovascular age-related macular degeneration.

Inhibition of inflammatory cells delays retinal degeneration in experimental retinal vein occlusion in mice.

The role of microglia in retinal inflammation is still ambiguous. Branch retinal vein occlusion initiates an inflammatory response whereby resident microglia cells are activated. They trigger infiltration of neutrophils that exacerbate blood-retina barrier damage, regulate postischemic inflammation and irreversible loss of neuroretina. Suppression of microglia-mediated inflammation might bear potential for mitigating functional impairment after retinal vein occlusion (RVO). To test this hypothesis, we depleted microglia by PLX5622 (a selective tyrosine kinase inhibitor that targets the colony-stimulating factor-1 receptor) in fractalkine receptor reporter mice (Cx3cr1gfp/+ ) subjected to various regimens of PLX5622 treatment and experimental RVO. Effectiveness of microglia suppression and retinal outcomes including retinal thickness as well as ganglion cell survival were compared to a control group of mice with experimental vein occlusion only. PLX5622 caused dramatic suppression of microglia. Despite vein occlusion, reappearance of green fluorescent protein positive cells was strongly impeded with continuous PLX5622 treatment and significantly delayed after its cessation. In depleted mice, retinal proinflammatory cytokine signaling was diminished and retinal ganglion cell survival improved by almost 50% compared to nondepleted animals 3 weeks after vein occlusion. Optical coherence tomography suggested delayed retinal degeneration in depleted mice. In summary, findings indicate that suppression of cells bearing the colony-stimulating factor-1 receptor, mainly microglia and monocytes, mitigates ischemic damage and salvages retinal ganglion cells. Blood-retina barrier breakdown seems central in the disease mechanism, and complex interactions between different cell types composing the blood-retina barrier as well as sustained hypoxia might explain why the protective effect was only partial.

AUTOMATED RETINAL LAYER SEGMENTATION AND THEIR THICKNESS PROFILES IN HEALTHY SUBJECTS: A Comparison of 55° Wide-field and Conventional 30° Spectral Domain-Optical Coherence Tomography.

PURPOSE: To assess whether retinal thickness measurements with a standard 30° spectral domain optical coherence tomography (SD-OCT) are comparable with wide-field 55° SD-OCT. METHODS: Thirty-three healthy individuals were scanned using 55° as well as 30° SD-OCT according to a standardized protocol. Automated retinal layer segmentation of standard and wide-field SD-OCTs was assessed using customized software. RESULTS: Both lenses showed a high correlation when analyzing total retinal thickness within the central, the inner, and the outer retinal ring (r = > 0.9). Automated thickness measurements with the 55° system were marginally higher compared with the 30° lens. The thickness of each separate retinal layer using automated segmentation showed excellent correlations within the inner and outer rings (range: r = 0.6-r = 0.9 for the inner ring and range: r = 0.9-r = 1.0 for the outer ring). CONCLUSION: Fifty-five degree wide-field SD-OCT provides a good overview of the posterior pole and presents similar quantitative values as a standard 30° OCT lens. Therefore, thickness values are comparable when switching between these two lenses.

FLUORESCENCE LIFETIME IMAGING OPHTHALMOSCOPY: Findings After Surgical Reattachment of Macula-Off Rhegmatogenous Retinal Detachment.

PURPOSE: The purpose of this study was to investigate fluorescence lifetime imaging ophthalmoscopy lifetimes after macula-off rhegmatogenous retinal detachment (RRD) repair. METHODS: Fifty-eight patients with successful macula-off RRD reattachment surgery were included. Retinal autofluorescence was excited with 470 nm, and amplitude-weighted mean fluorescence lifetimes (Tm) were measured in a short spectral channel (SSC, 498-560 nm) and a long spectral channel (LSC, 560-720 nm). Tm were obtained within a standardized Early Treatment Diabetic Retinopathy Study grid and correlated with Tm. The unaffected fellow eye served as control. RESULTS: Fifty-eight patients (age: 65 ± 1.6 years, 11 women) were imaged at median 1.5 months postoperatively. Tm were significantly prolongxxxed within areas of previously detached retina in the long spectral channel and particularly in the central subfield in the short spectral channel. Short lifetimes in the center of the Early Treatment Diabetic Retinopathy Study grid correlated with better visual acuity (short spectral channel; r = 0.18, P = 0.001, long spectral channel; r = 0.08, P = 0.03). Areas of residual subretinal fluid pockets in four RRD eyes displayed short fluorescence lifetimes. CONCLUSION: Areas of previously detached retina exhibit significant fluorescence lifetime changes. We found a significant correlation of fluorescence lifetimes within the fovea with visual acuity after successful RRD repair. Our data suggests that the prolongation of fluorescence lifetimes in the fovea is mainly driven by loss of macular pigment. Therefore, fluorescence lifetime imaging ophthalmoscopy may be useful in the prediction of long-term functional outcomes after macula-off RRD surgery.

EXIT STRATEGY IN A TREAT-AND-EXTEND REGIMEN FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To evaluate the outcome of an exit strategy in a treat-and-extend regimen for neovascular age-related macular degeneration. METHODS: Five hundred and ninety-eight eyes of 488 patients with neovascular age-related macular degeneration receiving intravitreal anti-vascular endothelial growth factor injections according to a treat-and-extend regimen were included in this retrospective study. A treat-and-extend regimen with either interval extension by 2 weeks or shortening by 1 week was used. "Exit criteria" were defined as 3 consecutive injections 16 weeks apart with stable findings after which the patient was exited from treatment and followed up at 3 to 4 monthly intervals without therapy. Best-corrected visual acuity, central retinal thickness at treatment initiation and termination, incidence of recurrence after treatment termination, presence of characteristics in the optical coherence tomography, duration of therapy, number and intervals of injections were analyzed. RESULTS: Seventeen percent of all included eyes met the exit criteria. The mean number of anti-vascular endothelial growth factor injections was 23.7 ± 14.7 with a mean treatment duration of 4.5 ± 2.5 years. Twelve percent reached exit with the minimal number of injections. Thirteen percent had recurrent disease after a mean of 37 ± 16 weeks. In the subgroup with recurrent disease, rate of pigment epithelial detachment at treatment termination was significantly higher than without recurrence (77% vs. 30%, P = 0.0018) with a significant higher proportion of serous pigment epithelial detachment (31% vs. 7%, P = 0.0247). CONCLUSION: The high percentage of patients meeting the exit criteria and the relatively low incidence of recurrences underline the usefulness of a predefined exit strategy. However, in a subgroup of patients, continuation of therapy may be advisable.

PATIENTS WITH EPIRETINAL MEMBRANES DISPLAY RETROGRADE MACULOPATHY AFTER SURGICAL PEELING OF THE INTERNAL LIMITING MEMBRANE.

PURPOSE: Intraretinal cystoid spaces are commonly found after surgical peeling of epiretinal membranes. In this study, we explored whether these cysts were associated with ganglion cell loss and thus might be a manifestation of retrograde maculopathy. The latter is a nonvascular edema with a characteristic morphology that is often found in the inner nuclear layer (INL) of patients with optic neuropathy. METHODS: In this retrospective case series, we identified consecutive patients who underwent surgical epiretinal membrane peeling. We determined the frequency of microcystic macular edema (MME), defined by vertical cystoid spaces in the INL, and we measured the thickness of individual macular layers before and after surgery. RESULTS: Epiretinal membrane peeling resulted in an improvement of visual acuity and a reduction of retinal thickness by about 15%. In total, 35% of patients with MME before surgery showed no sign of MME postoperatively, whereas edema persisted after surgery in 65% of patients. Interestingly, 29% of the patients without MME before surgery developed MME after surgery. Overall, we found MME in 35% of patients before peeling and in 42% after peeling. After surgery, the mean ganglion cell layer thickness was reduced compared with healthy control eyes. Ganglion cell layer thickness correlated inversely with thickness of the INL. Compared with patients without MME, individuals with MME had a thinner ganglion cell layer and a thicker INL in the affected eye. CONCLUSION: Our findings indicate that peeling of epiretinal membranes and internal limiting membranes is associated with atrophy of ganglion cells and thickening of the INL. The latter is associated with the presence of MME. Altogether, we assume that surgical treatment of epiretinal membranes induces a variant of a retrograde maculopathy.

One-Year Results of Using a Treat-and-Extend Regimen without a Loading Phase with Anti-VEGF Agents in Patients with Treatment-Naive Diabetic Macular Edema.

PURPOSE: To evaluate real-life outcomes in treatment-naive patients with diabetic macular edema (DME) treated with anti-vascular endothelial growth factor (VEGF) agents using a treat-and-extend regimen without a fixed loading phase. METHODS: Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) measured using optical coherence tomography at baseline and after 1 year of treatment, intervals and number of injections were analyzed. Subgroup analysis was performed to compare anatomical and functional outcomes between patients receiving ranibizumab or aflibercept. RESULTS: Seventy-five eyes of 61 patients met the inclusion criteria and had follow-up for 1 year. Baseline BCVA and CRT were 68.1 ± 13.2 letters and 424 ± 135 µm, retrospectively. After 1 year, there was a significant mean gain in BCVA of +5.8 ± 7.4 letters (paired t test: p < 0.0001) and a significant decrease in mean CRT of -117 ± 134 µm (paired t test: p < 0.0001). The mean number of anti-VEGF injections was 10.0 ± 1.6 (range 6-12). The mean maximum interval between injections was 8.5 ± 2.9 weeks (range 4-14) and the mean interval 6.0 ± 1.2 weeks (range 4.1-8.9). 96% of eyes could be extended after a mean of 5.3 injections and 17% of patients could be extended before reaching a formal loading dose of 3 injections. Subgroup analysis did not reveal any differences in outcomes between patients treated with ranibizumab or aflibercept. Subretinal fluid at baseline was associated with better BCVA gain after 1 year (stepwise forward regression analysis, p = 0.003). CONCLUSION: Our results suggest that not all patients with DME require a fixed loading phase when initiating anti-VEGF treatment. Finding anatomical predictors to identify this subgroup of patients would help to reduce treatment burden and optimize clinical outcomes.

Colony-stimulating factor 1 receptor inhibition prevents disruption of the blood-retina barrier during chronic inflammation.

BACKGROUND: Microglia-associated inflammation is closely related to the pathogenesis of various retinal diseases such as uveitis and diabetic retinopathy, which are associated with increased vascular permeability. In this study, we investigated the effect of systemic lipopolysaccharide (LPS) exposure to activation and proliferation of retinal microglia /macrophages. METHODS: Balb/c and Cx3cr1gfp/+ mice were challenged with LPS (1 mg/kg) daily for four consecutive days. For microglia depletion, mice were treated with colony-stimulating factor 1 receptor (CSF-1R) inhibitor PLX5622 1 week before the first LPS challenge and until the end of the experiment. In vivo imaging of the retina was performed on days 4 and 7 after the first LPS challenge, using optical coherence tomography and fluorescein angiography. Flow cytometry analysis, retinal whole mount, and retinal sections were used to investigate microglia and macrophage infiltration and proliferation after LPS challenge. Cytokines were analyzed in the blood as well as in the retina. Data analysis was performed using unpaired t tests, repeated measures one-way ANOVA, or ordinary one-way ANOVA followed by Tukey's post hoc analysis. Kruskal-Wallis test followed by Dunn's multiple comparison tests was used for the analysis of non-normally distributed data. RESULTS: Repeated LPS challenge led to activation and proliferation of retinal microglia, infiltration of monocyte-derived macrophages into the retina, and breakdown of the blood-retina barrier (BRB) accompanied by accumulation of sub-retinal fluid. Using in vivo imaging, we show that the breakdown of the BRB is highly reproducible but transitory. Acute but not chronic systemic exposure to LPS triggered a robust release of inflammatory mediators in the retina with minimal effects in the blood plasma. Inhibition of the CSF-1R by PLX5622 resulted in depletion of retinal microglia, suppression of cytokine production in the retina, and prevention of BRB breakdown. CONCLUSIONS: These findings suggest that microglia/macrophages play an important role in the pathology of retinal disorders characterized by breakdown of the BRB, and suppression of their activation may be a potential therapeutic target for such retinopathies.

Repeated Dexamethasone Intravitreal Implant for the Treatment of Diabetic Macular Oedema Unresponsive to Anti-VEGF Therapy: Outcome and Predictive SD-OCT Features.

PURPOSE: To investigate dexamethasone intravitreal implant 0.7 mg (DEX implant) for the treatment of diabetic macular oedema (DME) refractory to anti-vascular endothelial growth factor (anti-VEGF) therapy and evaluate predictive factors. METHODS: Two-centre retrospective interventional case series, including 40 eyes of 31 patients treated with DEX implant for at least 2 consecutive cycles. RESULTS: Mean ± SD intervals from implantation to recurrence in the first (4.2 ± 1.0 months) and second cycles (4.0 ± 0.9 months) were not significantly different. Best corrected visual acuity improved significantly (p < 0.001) by 7.0 ± 8.4 letters from baseline to month 2, and by 5.1 ± 6.9 letters between the first and second cycles. Central retinal thickness reduction 2 months after implantation was greater after the first (-194 ± 172 µm) than the second cycle (-134 ± 150 µm). Ellipsoid zone-external limiting membrane (EZ-ELM) disruption score decreased from 1.39 ± 1.16 at baseline to 1.24 ± 1.16 (p = 0.0832) after cycle 1 and remained stable 2 months after cycle 2. Eyes with persisting severe EZ-ELM disruption (score >2, n = 10) 2 months after the first DEX implant showed significantly (p = 0.0153) smaller visual acuity (VA) gains than eyes with less severe (score ≤2) EZ-ELM disruption. CONCLUSION: Repeated intravitreal DEX injections with average intervals of 4 months are valuable in patients with DME refractory to anti-VEGF therapy. Disorganization of outer retinal layers (EZ-ELM) may predict smaller VA gains if evaluated after initial reduction of macular oedema.

Imaging of macrophage dynamics with optical coherence tomography in anterior ischemic optic neuropathy.

Anterior ischemic optic neuropathy (AION) is a relatively common cause of visual loss and results from hypoperfusion of the small arteries of the anterior portion of the optic nerve. AION is the leading cause of sudden optic nerve related vision loss with approximately 10 cases per 100'000 in the population over 50 years. To date there is no established treatment for AION and therefore a better understanding of the events occurring at the level of the optic nerve head (ONH) would be important to design future therapeutic strategies. The optical properties of the eye allow imaging of the optic nerve in vivo, which is a part of the CNS, during ischemia. Experimentally laser induced optic neuropathy (eLiON) displays similar anatomical features as anterior ischemic optic neuropathy in humans. After laser induced optic neuropathy we show that hyperreflective dots in optical coherence tomography correspond to mononuclear cells in histology. Using fluorescence-activated flow cytometry (FACS) we found these cells to peak one week after eLiON. These observations were translated to OCT findings in patients with AION, where similar dynamics of hyperreflective dots at the ONH were identified. Our data suggests that activated macrophages can be identified as hyperreflective dots in OCT.

Comparison of two individualized treatment regimens with ranibizumab for diabetic macular edema.

PURPOSE: To compare outcomes between an as-needed and a treat-and-extend regimen in managing diabetic macular edema with intravitreal ranibizumab. METHODS: This was a retrospective, single-centre, comparative case series on 46 treatment naive patients with diabetic macular edema. Twenty-two patients were treated following an optical coherence tomography guided treat-and-extend protocol (OCTER), and 24 patients were treated according to a visual acuity guided pro re nata regimen (VAPRN) at a tertiarry referral centre. The main outcome measures were best-corrected visual acuity, central retinal thickness, and the number of ranibizumab injections, as well as visits after 12 months of treatment. RESULTS: After 12 months, the mean gain in best-corrected visual acuity (± standard deviation) was 8.3 ± 6.7 versus 9.3 ± 8.9 letters in the VAPRN and OCTER group, respectively (p = 0.3). The mean decrease in central retinal thickness was 68.1 ± 88.0 µm in the VAPRN group and 117.6 ± 114.4 µm in the OCTER group (p = 0.2). The mean number of ranibizumab injections was significantly different between the VAPRN (5.9 ± 1.8) and the OCTER protocol (8.9 ± 2.0) (p < 0.001). CONCLUSION: The visual acuity driven retreatment regimen resulted in a similar visual acuity outcome like optical coherence tomography guided retreatment for diabetic macular edema. Although the number of visits was similar in both groups, patients in the VAPRN group received significantly fewer intravitreal injections than patients in the OCTER group.

Atypical retinal pigment epithelial defects with retained photoreceptor layers: a so far disregarded finding in age related macular degeneration.

BACKGROUND: To report patients with age-related macular degeneration and atypical central retinal pigment epithelium (RPE) defects not attributable to geographic atrophy (GA) or RPE-tears with overlying preserved photoreceptor layers. METHODS: Multimodal imaging case-series evaluating the course of atypical RPE- defects in patients with AMD using Color fundus images, Optical coherence tomography (OCT), OCT-Angiography, fundus autofluorescence (FAF) and fluorescein-angiography (FA). RESULTS: Ten patients were identified. Three patients had a prior RPE-rip and were excluded. Seven patients with a mean follow-up period of 47 ± 38 months after the occurrence of the RPE-defect were included (age range 71-87 years). Mean distance Best corrected visual acuity (BCVA) at initial presentation was 0.36 ± 0.29logMAR and at last follow-up visit 0.51 ± 0.43logMAR. Patients presented with clinically apparent GA on funduscopy and FAF, but preserved photoreceptor layers on optical coherence tomography (OCT). On FA there was early hyperfluorescence and late pooling visible. Over time, migration of RPE/drusenoid material right above the Bruch's membrane with concomitant decrease of hypoautofluorescence was detectable in 4 cases. An enlargement of the RPE-defect was apparent in the remaining 3 cases. The majority (n = 4) showed a drusenoid pigment epithelium detachment (PED) preceding the lesion. CONCLUSIONS: Beside GA and characteristic RPE-tears, another atypical form of RPE-defect with overlying preserved photoreceptor layers are found in AMD. This so far disregarded subgroup of patients present with reasonable visual function and long-term survival of photoreceptors layers. Repair mechanisms such as ingrowth of RPE/drusenoid material and persistent subretinal fluid (SRF), but also a RPE-independent visual cycle for cone photopigment within the neurosensory retina may contribute to their favorable course.

Comparison of 55° Wide-Field Spectral Domain Optical Coherence Tomography and Conventional 30° Optical Coherence Tomography for the Assessment of Diabetic Macular Edema.

PURPOSE: To compare conventional 30° spectral domain optical coherence tomography (SD-OCT) with 55° wide-field SD-OCT for the assessment of diabetic macular edema (DME). METHODS: This study included 50 DME patients. Both 55° and 30° SD-OCT was conducted. Two readers evaluated scans according to a standardized grading protocol. Intergrader agreement as well as agreement between 30° and 55° SD-OCT were assessed. RESULTS: Intergrader agreement (κ) was strong and ranged from 0.79 to 1.0. Perfect interdevice agreement (κ = 1.0) was found for the detection of intra- and subretinal fluid. Excellent agreement (κ ≥ 0.9) was found for the presence of epiretinal membrane (κ = 0.92) and cotton-wool spots (κ = 0.92). A strong agreement was found for the presence of hard exudates (κ = 0.89) and microaneurysms (κ = 0.81). A moderate correlation was found for ellipsoid zone integrity (κ = 0.69) and configuration of the vitreomacular interface (VMI) (κ = 0.69). A weak agreement was found for retinal pigment epithelium atrophy (κ = 0.51) and external limiting membrane integrity (κ = 0.35). CONCLUSION: Wide-field OCT imaging may be beneficial for evaluating DME, particularly for assessing the VMI and the integrity of hyperreflective bands.

RETINAL LAYER RESPONSE TO RANIBIZUMAB DURING TREATMENT OF DIABETIC MACULAR EDEMA: Thinner is Not Always Better.

PURPOSE: To identify individual retinal layer thickness changes associated with visual acuity gain in diabetic macular edema treated with ranibizumab using layer segmentation on high-resolution optical coherence tomography scans. METHODS: Retrospective observational case series. Thirty-three treatment-naive eyes with diabetic macular edema were imaged by spectral domain optical coherence tomography at monthly visits while receiving intravitreal ranibizumab treatment as needed, guided by visual acuity. Thickness changes of individual layers after 1 year were quantitatively analyzed and correlated with visual acuity gain. RESULTS: The mean best-corrected visual acuity improvement at 1 year was 6.2 (SEM ± 1.5) Early Treatment Diabetic Retinopathy Study letters, and central retinal thickness decreased by 66 ± 18 µm. In the central subfield, there was a significant decrease of thickness for all layers (P < 0.05) except the outer nuclear layer. Multiple linear regression analysis revealed that thickness decrease of the inner retina was associated with better visual acuity, whereas for the outer retina the opposite was true. The best estimate of final visual acuity (R = 0.817, P < 0.001) was obtained, by including baseline visual acuity and thickness change of the inner and outer plexiform layers in the model. CONCLUSION: Whereas thickness decrease of the inner retina was positively associated with visual acuity gain, the opposite was found for the outer retina. This might be indirect evidence for recovery of the outer retina during ranibizumab treatment.

Fluctuations in Pigment Epithelial Detachment and Retinal Fluid Using a Bimonthly Treatment Regimen with Aflibercept for Neovascular Age-Related Macular Degeneration.

PURPOSE: To assess the effect of a bimonthly treatment regimen with intravitreal aflibercept on retinal fluid and pigment epithelial detachment (PED) in patients with neovascular age-related macular degeneration (AMD). METHODS: Twenty-six treatment-naive eyes of 26 patients with choroidal neovascularisation secondary to AMD were included. The patients received three initial monthly (mean 30 days) intravitreal injections of aflibercept followed by a bimonthly (mean 62 days) fixed regimen for a total of 1 year. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) measurements were recorded at monthly intervals. In addition, the presence of intraretinal fluid (IRF) or subretinal fluid (SRF) or a combination of both as well as serous and fibrovascular PEDs were assessed. RESULTS: The mean patient age was 80 years (range 54-93). There were 14 male and 12 female patients. The mean gain in BCVA at 1 year was 9.3 letters (SEM ±3) with a mean reduction of the central retinal thickness of 154 µm (SEM ±50). After 3 monthly injections of aflibercept, there was resolution of IRF and SRF in 80% of the treated eyes; the amount of fluid increased at months 4, 6 and 8 with troughs in between. Whereas fibrovascular PEDs remained stable after the loading phase, serous PEDs displayed a seesaw pattern. Patients without retinal pigment epithelium (RPE) atrophy at the end of the 1-year period had significantly better BCVA compared to patients with RPE atrophy (p = 0.03). CONCLUSION: Despite significant overall BCVA gain, bimonthly intervals seem insufficient to maintain the morphological improvements after the initial loading dose with intravitreal aflibercept.

Outcomes when Switching from a pro re nata Regimen to a Treat and Extend Regimen Using Aflibercept in Neovascular Age-Related Macular Degeneration.

PURPOSE: To investigate outcomes in patients with neovascular age-related macular degeneration (AMD) switched from a pro re nata regimen (PRN) to a treat and extend regimen (TER) under aflibercept. PROCEDURE: Thirty-two patients were observed over 2 years: the first year on PRN and the second year on TER. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were evaluated. Intra- and subretinal fluid as well as the number of visits and injections were assessed. RESULTS: Both regimens resulted in a stable BCVA. Patients in TER had a significant decrease of CRT after 1 year compared to 1 year of treatment on PRN (p < 0.0001). TER resulted in significantly less visits; however, significantly more injections were observed over the course of 1 year compared to PRN (10.25 vs. 7.5, p < 0.0001 and 5.97 vs. 7.5, p = 0.0002, respectively). CONCLUSION: A switch from PRN to TER in patients treated with aflibercept for AMD appears to be safe.

Metrics of the normal anterior sclera: imaging with optical coherence tomography.

BACKGROUND: To investigate anterior scleral thickness in a cohort of healthy subjects using enhanced depth imaging anterior segment optical coherence tomography. METHODS: Observational case series. The mean scleral thickness in the inferonasal, inferotemporal, superotemporal, and superonasal quadrant was measured 2 mm from the scleral spur on optical coherence tomography in healthy volunteers. RESULTS: Fifty-three eyes of 53 Caucasian patients (25 male and 28 female) with an average age of 48.6 years (range: 18 to 92 years) were analysed. The mean scleral thickness was 571 µm (SD 84 µm) in the inferonasal quadrant, 511 µm (SD 80 µm) in the inferotemporal quadrant, 475 (SD 81 µm) in the superotemporal, and 463 (SD 64 µm) in the superonasal quadrant. The mean scleral thickness was significantly different between quadrants (p < 0.0001, repeated measures one-way ANOVA). The association between average scleral thickness and age was statistically significant (p < 0.0001, Pearson r = 0.704). CONCLUSIONS: Enhanced depth imaging optical coherence tomography revealed the detailed anatomy of the anterior sclera and enabled non-invasive measurements of scleral thickness in a non-contact approach. The anterior scleral thickness varies significantly between quadrants, resembling the spiral of Tillaux. An association of increasing scleral thickness with age was found.

The Presence of Intra- or Subretinal Fluid during the Loading Phase in the Treatment of Exudative Age-Related Macular Degeneration with Intravitreal Ranibizumab Assessed by Optical Coherence Tomography.

PURPOSE: To assess intra- and subretinal fluid during the loading phase with intravitreal ranibizumab in exudative age-related macular degeneration and to quantify the accuracy of crosshair scan spectral-domain optical coherence tomography with regard to retinal fluid. METHODS: This is a retrospective study of 31 treatment-naive patients who received 3 monthly intravitreal ranibizumab injections. Visual acuity and the presence of retinal fluid were assessed at each visit using volume and crosshair scan protocols. RESULTS: Visual acuity improved and central retinal thickness decreased significantly during the loading phase. However, retinal fluid persisted in two thirds of the patients. The accuracy of the crosshair scan to detect fluid was 93%. CONCLUSIONS: A substantial proportion of eyes had persistent fluid after 3 months of ranibizumab injections. However, visual improvement was independent of residual fluid. MESSAGE: Crosshair scans detect relevant collections of retinal fluid accurately and may be sufficient in daily clinical practice.

Glucose-induced temporary visual recovery in primary open-angle glaucoma: a double-blind, randomized study.

PURPOSE: To investigate the effect of topical glucose on visual parameters in individuals with primary open-angle glaucoma (POAG). DESIGN: Double-blind, randomized, crossover study. PARTICIPANTS: Nondiabetic pseudophakic patients with definite POAG were recruited; 29 eyes of 16 individuals participated in study 1. A follow-up study (study 2) included 14 eyes of 7 individuals. INTERVENTION: Eyes were randomly allocated to receive 50% glucose or saline eye drops every 5 minutes for 60 minutes. MAIN OUTCOME MEASURES: The contrast sensitivity and best-corrected logarithm of the minimum angle of resolution (logMAR). RESULTS: The 50% glucose reached the vitreous in pseudophakic but not phakic individuals. Glucose significantly improved the mean contrast sensitivity at 12 cycles/degree compared with 0.9% saline by 0.26 log units (95% confidence interval [CI], 0.13-0.38; P < 0.001) and 0.40 log units (95% CI, 0.17-0.60; P < 0.001) in the follow-up study. The intraocular pressure, refraction, and central corneal thickness were not affected by glucose; age was not a significant predictor of the response. CONCLUSIONS: Topical glucose temporarily improves psychophysical visual parameters in some individuals with POAG, suggesting that neuronal energy substrate delivery to the vitreous reservoir may recover function of "sick" retinal neurons.