Potential impact of fluorescein angiography as a primary imaging modality in the management of diabetic retinopathy.

Purpose: To evaluate current practice patterns for Egyptian ophthalmologists in the diagnosis of diabetic retinopathy (DR) and explore potential implications of these approaches on management. Methods: Cross-sectional survey conducted in Egypt amongst practicing ophthalmologists. Results: The study had 203 responses (~6% of all Egyptian ophthalmologists). A majority of respondents were general ophthalmologists (78.2%), practicing for five to ten years (41.9%). In patients with DR and no diabetic macular edema (DME), 33.0% of respondents would use FA in patients with mild DR, 44.3% in patients with moderate DR and 51.2% in patients with severe non-proliferative diabetic retinopathy (NPDR). Color imaging (CI) was used by less than 1% as the sole imaging modality for any level of DR. Approximately 70% of respondents used fluorescein angiography (FA) to grade and base treatment decisions for DR, either alone or in conjunction with dilated eye exams and/or CI. Given the known more severe appearance of DR on FA than on standard color imaging upon which treatment guidelines are based, use of FA as the primary modality over a one-year period could result in PRP that would otherwise not be suggested in approximately 78,820 eyes at an additional cost of $10.1 million US dollars. These numbers are projected to double by 2045. Conclusion: Given that FA detects significantly greater pathology than CI, and that treatment and follow-up recommendations are based on CI, its use as the primary imaging modality in DR grading may result in apparently significantly higher DR severity, with subsequently increased procedures and associated costs.

Factors Affecting Predominantly Peripheral Lesion Identification and Grading.

Purpose: The purpose of this study was to determine factors affecting predominantly peripheral lesion (PPL) grading, such as qualitative versus quantitative assessment, device type, and severity of diabetic retinopathy (DR) in ultrawide field color images (UWF-CIs). Methods: Patients with DR had UWF-CI qualitatively graded for PPL using standardized techniques and had hemorrhages/microaneurysms (H/Mas) individually annotated for quantitative PPL grading on two different ultrawide field devices. Results: Among 791 eyes of 481 patients, 38.2% had mild nonproliferative DR (NPDR), 34.7% had moderate NPDR, and 27.1% had severe NPDR to proliferative DR (PDR). The overall agreement between qualitative and quantitative PPL grading was moderate (ĸ = 0.423, P < 0.001). Agreement rates were fair in eyes with mild NPDR (ĸ = 0.336, P < 0.001) but moderate in eyes with moderate NPDR (ĸ = 0.525, P < 0.001) and severe NPDR-PDR (ĸ = 0.409, P < 0.001). Increasing thresholds for quantitative PPL determination improved agreement rates, with peak agreements at H/Ma count differences of six for mild NPDR, five for moderate NPDR, and nine for severe NPDR-PDR. Based on ultrawide field device type (California = 412 eyes vs. 200Tx = 379 eyes), agreement between qualitative and quantitative PPL grading was moderate for all DR severities in both devices (ĸ = 0.369-0.526, P < 0.001) except for mild NPDR on the 200Tx, which had poor agreement (ĸ = 0.055, P = 0.478). Conclusions: Determination of PPL varies between standard qualitative and quantitative grading and is dependent on NPDR severity, device type, and magnitude of lesion differences used for quantitative assessment. Translational Relevance: Prior UWF studies have not accounted for imaging and grading factors that affect PPL, such factors need to be reviewed when assessing thresholds for DR progression rates.

Pars Plana Vitrectomy versus Intravitreal Injection of Ranibizumab in the Treatment of Diabetic Macular Edema Associated with Vitreomacular Interface Abnormalities.

PURPOSE: To compare the efficacy of pars plana vitrectomy (PPV) versus intravitreal injection (IVI) of ranibizumab (RBZ) in the treatment of diabetic macular edema (DME) associated with vitreomacular interface abnormalities (VMIA). METHODS: The records of patients presenting with DME and VMIA throughout 2016 to 2018 were retrospectively analyzed. The patients were divided into 2 groups: group I received IVIs of RBZ and group II underwent PPV with internal limiting membrane peeling. The main outcome measures were the change in the LogMAR corrected distance visual acuity (CDVA) and central subfield thickness (CSFT) on optical coherence tomography over 6 months. RESULTS: At 6 months, mean CDVA improved by 0.22 ± 0.21 in group I patients (p < 0.001), while in group II, it improved only by 0.09 ± 0.22 (p < 0.115). Fifty-five percent of group I and 60% of group II patients had stable CDVA (within 2 lines from baseline) at 6 months. Significant improvement in vision (gain of 2 or more lines) was seen in 45% and 30%, respectively. Worsening of vision (loss of 2 or more lines) was seen only in 2 patients in group II, but none in group I. The mean CSFT improved significantly in both groups (by 162 µ and 216 µ, respectively; p < 0.001). The mean CSFT at 6 months was similar in both groups (354 µ and 311 µ, respectively; p=0.172). CONCLUSIONS: Both treatments resulted in anatomical improvement of DME with concurrent VMIA. Visual improvement was more pronounced in the IVI group, although this may have been affected by other confounding factors.

An Unusual Sticky Situation of New-Onset Right Sided Heart Failure.

This case highlights the importance of having constrictive pericarditis (CP) as a differential diagnosis in unexplained sign and symptoms of right-sided heart failure. This case portrays challenges in diagnosing CP caused by certain rheumatologic diseases despite advances in diagnostic modalities, clinical suspicion remains the most important tool for this diagnosis.

Disparity of microaneurysm count between ultrawide field colour imaging and ultrawide field fluorescein angiography in eyes with diabetic retinopathy.

AIMS: To compare microaneurysm (MA) counts using ultrawide field colour images (UWF-CI) and ultrawide field fluorescein angiography (UWF-FA). METHODS: Retrospective study including patients with type 1 or 2 diabetes mellitus receiving UWF-FA and UWF-CI within 2 weeks. MAs were manually counted in individual Early Treatment Diabetic Retinopathy Study (ETDRS) and extended UWF zones. Fields with MAs ≥20 determined diabetic retinopathy (DR) severity (0 fields=mild, 1-3=moderate, ≥4=severe). UWF-FA and UWF-CI agreement was determined and UWF-CI DR severity sensitivity analysis adjusting for UWF-FA MA counts performed. RESULTS: In 193 patients (288 eyes), 2.4% had no DR, 29.9% mild non-proliferative DR (NPDR), 32.6% moderate (NPDR), 22.9% severe NPDR and 12.2% proliferative DR. UWF-FA MA counts were 3.5-fold higher (p<0.001) than UWF-CI counts overall, 3.2x-fold higher in ETDRS fields (p<0.001) and 5.3-fold higher in extended ETDRS fields (p<0.001) and higher in type 1 versus type 2 diabetes (p<0.001). In eyes with NPDR on UWF-CI (n=246), UWF-FA images had 1.6x-3.5x more fields with ≥20 MAs (p<0.001). Fair agreement existed between imaging modalities (k=0.221-0.416). In ETDRS fields, DR severity agreement increased from k=0.346 to 0.600 when dividing UWF-FA counts by a factor of 3, followed by rapid decline in agreement thereafter. Total UWF area agreement increased from k=0.317 to 0.565 with an adjustment factor of either 4 or 5. CONCLUSIONS: UWF-FA detects threefold to fivefold more MAs than UWF-CI and identifies 1.6-3.5-fold more fields affecting DR severity. Differences exist at all DR severity levels, thus limiting direct comparison between the modalities. However, correcting UWF-FA MA counts substantially improves DR severity agreement between the modalities.

Intravitreal ziv-aflibercept in diabetic vitreous hemorrhage.

BACKGROUND: To evaluate the safety and efficacy of intravitreal ziv-aflibercept (IVZ) in the management of vitreous hemorrhage (VH) in eyes with previously lasered proliferative diabetic retinopathy (PDR). METHODS: In a prospective multicenter study, previously lasered eyes who had dense VH from PDR underwent intravitreal injection of ziv-aflibercept (IVZ) (1.25 mg aflibercept). Demographic characteristics of the patients, baseline and final logMar visual acuity, number of injections, VH clearance time, and need for vitrectomy were recorded. RESULTS: Twenty-seven eyes of 21 patients were included in the study. Mean age of study patients was 61.3 ± 14.1 years with mean duration of diabetes mellitus of 22.6 ± 7.8 years. Mean logMAR BCVA at baseline was 1.41 ± 1.26 (Snellen equivalent 20/514) and at the last visit 0.55 ± 0.61 (Snellen equivalent 20/70) with a mean gain of 0.86 EDTRS line (paired student t test = 5.1; p ≤ 0.001). Mean number of IVZ 2.4 ± 1.6 (range 1-6). The mean follow-up time was 11.7 ± 11.1 months (range 1-34). Mean time for visual recovery and/or VH clearance was 5.7 ± 3.3 weeks. Eyes, which required multiple injections, the interval period between injections for recurrent VH was 6.4 ± 5.2 months. No subject required vitrectomy. No ocular or systemic adverse effects were noted. CONCLUSIONS: IVZ injections had good short-term safety and efficacy for the therapy of new or recurrent VH in previously lasered eyes with PDR reducing somewhat the need for vitrectomy.Trial registration: NCT02486484.

Safety of 5914 intravitreal ziv-aflibercept injections.

PURPOSE: To analyse the pooled safety data of intravitreal ziv-aflibercept (IVZ) therapy for various retinal conditions. METHODS: This was a retrospective, observational study which included patients from 14 participating centres who received IVZ. The medical records of patients who received IVZ from March 2015 through October 2017 were evaluated. Patient demographics and ocular details were compiled. Ocular and systemic adverse events that occurred within 1 month of IVZ injections were recorded and defined as either procedure-related or drug-related. RESULTS: A total of 1704 eyes of 1562 patients received 5914 IVZ injections (mean±SD: 3.73±3.94) during a period of 2.5 years. The age of patients was 60.6±12.8 years (mean±SD) and included diverse chorioretinal pathologies. Both ocular (one case of endophthalmitis, three cases of intraocular inflammation, and one case each of conjunctival thinning/necrosis and scleral nodule) and systemic adverse events (two cases of myocardial infarction, one case of stroke and two deaths) were infrequent. CONCLUSION: This constitutes the largest pooled safety report on IVZ use and includes patients from 14 centres distributed across the globe. It shows that IVZ has an acceptable ocular and systemic safety profile with incidences of adverse events similar to those of other vascular endothelial growth factor inhibitory drugs. The analysis supports the continued use of IVZ in various retinal disorders.

Two-year outcomes of intravitreal ziv-aflibercept.

AIM: To assess the two-year outcome of intravitreal ziv-aflibercept (IVZ) in eyes with macular diseases. METHODS: Consecutive subjects with various macular diseases that received six or more of 0.05 mL IVZ (1.25 mg) injections with at least 1 year follow-up were included. Outcome measures were best-corrected visual acuity (BCVA) (logarithm of the minimum angle of resolution) and central macular thickness (CMT) on spectral domain optical coherence tomography. Paired comparison was done using Wilcoxon signed-rank test calculator. RESULTS: 107 eyes of 91 subjects received IVZ and were followed with mean±SD follow-up interval of 1.48±0.44 months following treat and extend or pro-re-nata protocol. The distribution included neovascular macular degeneration (42 eyes), diabetic macular oedema (32 eyes) and macular oedema secondary to retinal vein occlusion (11 eyes). Fifty eyes were naive, while 57 eyes were previously treated. Combining all disease categories, CMT decreased significantly by 133.0±153.0 µm at the 24-month follow-up (P<0.001) with BCVA gain of 0.35±0.37 at the 24-month follow-up (P<0.001) with mean number of injections of 8.5 at month 12, 2.4 between 12 and 18 month and 1.7 between 18 and 24 month. Ocular and systemic adverse effects included one episode of transient uveitis and one instance of central retinal artery occlusion after 1121 injections. CONCLUSIONS: IVZ appears safe and efficacious in the therapy of macular diseases through 2 years.

Age-related macular degeneration: using morphological predictors to modify current treatment protocols.

To assess predictors of treatment response in neovascular age-related macular degeneration (AMD) in an attempt to develop a patient-centric treatment algorithm. We conducted a systematic search using PubMed, EMBASE and Web of Science for prognostic indicators/predictive factors with the key words: 'age related macular degeneration', 'neovascular AMD', 'choroidal neovascular membrane (CNV)', 'anti-vascular endothelial growth factor (anti-VEGF)', 'aflibercept', 'ranibizumab', 'bevacizumab', 'randomized clinical trials', 'post-hoc', 'prognostic', 'predictive', 'response' 'injection frequency, 'treat and extend (TAE), 'pro re nata (PRN)', 'bi-monthly' and 'quarterly'. We only included studies that had an adequate period of follow-up (>1 year), a single predefined treatment regimen with a predetermined re-injection criteria, an adequate number of patients, specific morphological [optical coherence tomography (OCT)] criteria that predicted final visual outcomes and injection frequency and did not include switching from one drug to the other. We were able to identify seven prospective studies and 16 retrospective studies meeting our inclusion criteria. There are several morphological and demographic prognostic indicators that can predict response to therapy in wet AMD. Smaller CNV size, subretinal fluid (SRF), retinal angiomatous proliferation (RAP) and response to therapy at 12 weeks (visual, angiographic or OCT) can all predict good visual outcomes in patients receiving anti-VEGF therapy. Patients with larger CNV, older age, pigment epithelial detachment (PED), intraretinal cysts (IRC) and vitreomacular adhesion (VMA) achieved less visual gains. Patients having VMA/VMT required more intensive treatment with increased treatment frequency. Patients with both posterior vitreous detachment (PVD) and SRF require infrequent injections. Patients with PED are prone to recurrences of fluid activity with a reduction in visual acuity (VA). A regimen that involves less intensive therapy and extended follow-up intervals (4 weekly) can be suggested for patients who show adequate visual response and have both SRF and PVD at baseline. In addition, patients with poor prognostic indicators such as IRC, VMA, large CNV size, older age and poor response at 12 weeks should be extended very cautiously with the possibility of fixed monthly/bimonthly (every 2 months) treatments if they fail to achieve dryness. Patients with PED at baseline should receive monthly/bimonthly injections of anti-VEGF therapy or can be extended very cautiously (two weekly intervals) using a TAE protocol.

Safety and Efficacy of Ziv-Aflibercept in the Treatment of Refractory Diabetic Macular Edema.

BACKGROUND AND OBJECTIVE: To evaluate the safety and efficacy of ziv-aflibercept (Zaltrap; Sanofi-Aventis, Bridgewater, NJ/Regeneron Pharmaceuticals, Tarrytown, NY) in the treatment of refractory diabetic macular edema (DME). PATIENTS AND METHODS: Retrospective case series looking at the safety of ziv-aflibercept in patients with DME refractory to previous anti-vascular endothelial growth factor (VEGF) therapy. Detailed ophthalmologic examination, best-corrected visual acuity, and optical coherence tomography measurements were performed pre-switch, as well as at each monthly follow-up visit. RESULTS: The study included 34 eyes of 26 patients. The mean number of ziv-aflibercept injections post-switch was 2.03 injections. Visual acuity improved from a mean of 0.63 logMAR pre-switch to 0.51 logMAR after the first visit and 0.46 logMAR after the second visit post-switch (P < .084). Macular thickness improved from a mean of 513.79 µm to 411.79 µm (P = .006) on the first visit and 426.76 µm (P = .029) after the second visit post-switch. No adverse ocular or systemic side effects were reported on any of the follow visits. CONCLUSION: Ziv-aflibercept appears to be safe and effective in patients with refractory DME previously treated with other anti-VEGF agents in the short term. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:399-405.].

Short-Term Effects of Early Switching to Ranibizumab or Aflibercept in Diabetic Macular Edema Cases With Non-Response to Bevacizumab.

BACKGROUND AND OBJECTIVES: To study the effect of early switching to ranibizumab (Lucentis; Genentech, South San Francisco, CA) or aflibercept (Eylea; Regeneron, Tarrytown, NY) in cases of diabetic macular edema (DME) that have shown no response to bevacizumab (Avastin; Genentech, South San Francisco, CA). PATIENTS AND METHODS: A retrospective study involving 59 eyes of 45 patients with DME previously treated with bevacizumab. Patients were switched either to ranibizumab or aflibercept. Detailed ophthalmological examination, best-corrected visual acuity (BCVA), and optical coherence tomography (Spectralis; Heidelberg Engineering, Heidelberg, Germany) were performed prior to and 1 month post-switch. RESULTS: Fifty-nine eyes of 45 patients were included in the study, of whom 14 patients (17 eyes) were switched to aflibercept and 31 patients (42 eyes) were switched to ranibizumab. Post-switch, there was a statistically significant improvement in the BCVA in the combined group (aflibercept and ranibizumab), as well as in the ranibizumab group alone. In addition, there was a statistically significant decrease in the central subfield thickness (CST) in the combined group, as well as in the ranibizumab and aflibercept groups individually. There was no significant difference with regard to the change in macular thickness or BCVA between the aflibercept and ranibizumab groups. In addition, neither the pre-switch central macular thickness, previous number of injections, nor the pre-switch visual acuity affected the response to switching. CONCLUSION: Aflibercept and ranibizumab both appear to be effective for patients showing no initial response to bevacizumab. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:230-236.].

Long-term safety and efficacy of ziv-aflibercept in retinal diseases.

AIMS: To investigate the long-term safety of intravitreal ziv-aflibercept in eyes receiving six or more intravitreal injections of ziv-aflibercept, an off-label substitute to the approved aflibercept. METHODS: Consecutive patients with retinal disease receiving six or more of intravitreal 0.05 mL ziv-aflibercept (1.25 mg) injections were followed monthly in three centres. Outcome measures were best-corrected visual acuity (BCVA) (logarithm of the minimum angle of resolution (logMar)) and central macular thickness (CMT) on spectral domain optical coherence tomography and monitoring for ocular inflammation, progression of lens opacities and intraocular pressure rise. Paired comparison was done using Wilcoxon signed-rank test calculator. RESULTS: Sixty-five eyes of 60 consecutive patients received a mean of 8.4 (6-17) intravitreal injections with a baseline mean logMAR BCVA of 0.98±0.56 and CMT 432.7±163.0 µm and followed for a mean of 9.2 months (range 6-18 months). After the sixth injection, mean BCVA improved to 0.57±0.36 (p=0.001) and CMT decreased to 274.8±117.8 µm (p=0.0001). At the 9-month follow-up, mean BCVA improved to 0.62±0.37 (p=0.0004) and mean CMT decreased to 292.0±160.9 µm (p<0.01) in 19 eyes. At 1 year, mean BCVA was 0.73±0.52 and CMT 311.6±232.5 µm in seven eyes. Intraocular pressures did not increase after injections. One subject developed transient mild iritis at the fourth injection but not on subsequent injections. No lens opacity progression or endophthalmitis was noted. Systemic adverse effects were not registered. CONCLUSIONS: Repeated intravitreal injections of ziv-aflibercept appear tolerable, safe and efficacious in the therapy of retinal disease.

ASSOCIATION BETWEEN THE VITREOMACULAR INTERFACE AND OPTICAL COHERENCE TOMOGRAPHY CHARACTERISTICS IN WET AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To study the effect of the vitreomacular interface on various wet age-related macular degeneration (AMD) characteristics including the size and type of choroidal neovascularization (CNV), choroidal thickness, and activity of the CNV. METHODS: This was a retrospective observational cross-sectional study. The study included 43 patients (51 eyes) with treatment-naive age-related macular degeneration. Twenty-six patients with wet AMD in one eye and dry AMD in the other eye were included in a paired-eye analysis. Patients underwent optical coherence tomography examination using Heidelberg Spectralis (spectral domain optical coherence tomography) at presentation to determine the type of CNV and the vitreomacular status. In addition, various parameters were measured including the choroidal thickness and horizontal width and vertical height measurements of the CNV. RESULTS: There was no correlation between the height, width, activity or type of the CNV, and the presence or absence of vitreomacular adhesion. The mean choroidal thickness (using enhanced depth imaging) in cases with vitreomacular adhesion was 272.57 µm compared with 197.32 µm in cases with no vitreomacular adhesion, a statistically significant difference (P = 0.003). In the paired-eye study (21 patients), there was no significant difference between the eyes with wet AMD and dry AMD with regard to vitreomacular status or the choroidal thickness. In a subgroup analysis, patients with Type 1 CNV had a significantly higher percentage of vitreomacular adhesion compared with the other eye with dry AMD (P = 0.034). CONCLUSION: In conclusion, the vitreomacular interface does seem to be associated with an increased choroidal thickness in cases of wet AMD. Furthermore, the association between the vitreomacular interface and wet AMD is more significant for Type 1 CNV.

Predicting outcomes to anti-vascular endothelial growth factor (VEGF) therapy in diabetic macular oedema: a review of the literature.

Diabetic macular oedema affects visual acuity to a varying degree. The current treatment of choice is intravitreal anti-vascular endothelial growth factor (VEGF) that has proven both its anatomical and visual efficacy in several large randomised clinical trials (RCTs). Although most patients respond well to anti-VEGF agents, some, however, show a moderate or even poor response. There is no clear consensus as to how to manage these patients, or define them. In addition, identifying early in the course of treatment which patients will respond and which patients will not is paramount to any personalised treatment regimen. Most large RCTs such as RESTORE and Protocol I have attempted post hoc analyses to identify demographic, clinical, optical coherence tomography (OCT) and fluorescein angiography findings that might predict patient response. Although some factors were found to be predictive, the lack of uniformity between the different RCTs means that no consensus exists as to which of these factors can be reliably used. This review looks at the large diabetic macular oedema RCTs such as RESTORE, Protocol I, READ-2 and BOLT in an attempt to identify common prognostic indicators between the various studies. We also attempted to look at several other OCT parameters such as the inner segment-outer segment (IS-OS) layer, the external limiting membrane layer, and choroidal thickness to help determine whether they can truly predict visual outcomes in patients being treated with anti-VEGF therapy. Finally, we provide a simplified summary about which factors might be relevant in clinical practice to help guide physicians in treatment decisions.

Steroids in Central Retinal Vein Occlusion: Is There a Role in Current Treatment Practice?

With the current widespread use of anti-VEGFs in the treatment of central retinal vein occlusion (CRVO), the role for steroids has become greatly diminished. Recent large scale randomized control trials (RCTs) have established the efficacy and safety of anti-VEGFs in the treatment of CRVO. Steroids are known to cause elevations in intraocular pressure as well as increase the risk of cataract formation. With that in mind many ophthalmologists are injecting steroids less frequently. This paper aims to review some of the data pertaining to the use of steroids either as a first line monotherapy, adjunct therapy, or an alternative therapy to help answer the question: Is there currently any role for steroids in the management of CRVO?

Correlation between optical coherence tomography and autofluorescence in acute posterior multifocal placoid pigment epitheliopathy.

PURPOSE: To report a case of bilateral acute posterior multifocal placoid pigment epitheliopathy (APMPPE) evaluated by optical coherence tomography (OCT), fundus autofluorescence (AF) and microperimetry, both in the acute phase and after resolution of symptoms. METHODS: Complete ophthalmological evaluation, including fluorescein angiography, OCT, AF, and microperimetry upon presentation and 1 month later, after lesions have subsided. An attempt to correlate the findings on presentation and changes after resolution is performed using the results of these new investigational techniques. RESULTS: APMPPE showed hyperreflectance in OCT at the level of the outer retinal layers, without increase in retinal thickness. AF revealed early decreased fluorescence due to a masking effect, and later reveals increased fluorescence after resolution of OCT findings. Function is disturbed at the lesion sites, as shown by microperimetry, and later returns to near normal values on microperimetry. CONCLUSION: APMPPE shows outer retinal layers changes on OCT, which resolve totally after subsidence of the acute phase. AF shows areas of increased fluorescence after resolution, with near normal return of function on microperimetry.