Is diabetic retinopathy screening worthwhile among people first diagnosed with diabetes at older ages? A cohort study of Norfolk diabetic retinopathy screening programme.

AIMS: England's Diabetic Eye Disease Screening Programme offers screening to every resident over age 12 with diabetes, starting as soon as possible after diagnosis and repeated annually. People first diagnosed with diabetes at older ages have shorter life expectancy and therefore may be less likely to benefit from screening and treatment. To inform decisions about whether diabetic eye screening policy should be stratified by age, we investigated the probability of receiving treatment according to age at first screening episode. METHODS: This was a cohort study of participants in the Norfolk Diabetic Retinopathy Screening Programme from 2006 to 2017, with individuals' programme data linked to hospital treatment and death data recorded up to 2021. We estimated and compared the probability, annual incidence and screening costs of receiving retinal laser photocoagulation or intravitreal injection and of death, in age groups defined by age at first screening episode. RESULTS: The probability of death increased with increasing age at diagnosis, while the probability of receiving either treatment decreased with increasing age. The estimated cost of screening per person who received either or both treatments was £18,608 among all participants, increasing with age up to £21,721 in those aged 70-79 and £26,214 in those aged 80-89. CONCLUSIONS: Diabetic retinopathy screening is less effective and less cost-effective with increasing age at diagnosis of diabetes, because of the increasing probability of death before participants develop sight-threatening diabetic retinopathy and can benefit from treatment. Upper age limits on entry into screening programmes or risk stratification in older age groups may, therefore, be justifiable.

Effect of intravitreal injections due to neovascular age-related macular degeneration on retinal nerve fiber layer thickness and minimum rim width: a cross sectional study.

PURPOSE: The present study tested the hypothesis that repeated anti-VEGF injections are associated with reduced retinal nerve fiber layer (RNFL) and minimum rim width (MRW) of the optic nerve head. PATIENTS AND METHODS: Sixty-six patients with a history of intravitreal injections due to neovascular age-related macular degeneration were included. RNFL and MRW were measured using optical coherence tomography (Spectralis OCT, Heidelberg Engineering, Heidelberg, Germany). RESULTS: Mean global RNFL was 90.62 µm and both RNFL as well as MRW significantly decreased with advanced age (p = 0.005 and p = 0.019, respectively). Correlating for the number of injections, no significant impact on RNFL was found globally (p = 0.642) or in any of the sectors. In contrast, however, global MRW was significantly reduced with increasing numbers of intravitreal injections (p = 0.012). The same holds true when adjusted for the confounding factor age (RNFL p = 0.566 and MRW p = 0.023). CONCLUSION: Our study shows that repeated intravitreal injections due to choroidal neovascularization seem to have a deleterious effect on MRW but not on RNFL. This suggests that MRW is a more sensitive marker than RNFL for evaluating the effect of frequent intravitreal injections on the optic nerve head since it seems to be the first structure affected.

Disease quiescence in endophthalmitis patients treated with anti-VEGF injections for retinal pathologies.

BACKGROUND: The most feared complication of intravitreal injections is the development of endophthalmitis, which could lead to irreversible visual loss. The aim of this study was to characterize the clinical profiles, causative pathogens, and clinical outcome of patients post-endophthalmitis. METHODS: Retrospective, single center case series study. Clinical records, causative pathogens and management of all cases of endophthalmitis post intravitreal anti-vascular endothelial growth factor (VEGF) injections recorded between January 1st, 2006 and May 30th, 2022; were retrieved. The visual and anatomic changes prior to the episode of endophthalmitis and up to 2 years post-treatment were compared. RESULTS: Eleven post-injection endophthalmitis eyes of 10 patients (n = 3 females; 30%) were recruited at mean age of 64.5 ± 20.4 years. The median last recorded BCVA, up to 3 months prior to the episode of endophthalmitis was 60 (Interquartile range (IQR) 55-75) ETDRS letters. Then, it dropped to 30 (IQR 0-57.5), 35 (IQR 0-52.5) and 35 (IQR 0-57.5) ETDRS letters at presentation, 6- and 12-months follow-up; respectively (p = 0.027, p = 0.017 and p = 0.012). However, at 24 months, the median BCVA returned to similar baseline values prior to the episode of endophthalmitis; BCVA 50 (IQR 0-60) ETDRS letters, p = 0.062. Interestingly, two eyes with neovascular age-related macular degeneration (NVAMD), 1 with myopic choroidal neovascularization (CNV) and 1 with retinal vein occlusion (RVO), experienced disease quiescence and did not require additional anti-VEGF injections up to 2 years of follow-up. CONCLUSION: This study demonstrates long-term recovery of vision loss due to endophthalmitis post anti-VEGF injections, regained up to 2 years later. It also indicates that disease quiescence post endophthalmitis may not only occur in eyes treated for NVAMD, but also with myopic CNV and RVO.

[Application of optical coherence tomography in the assessment of the posterior lens capsule during anti-angiogenic therapy]. / Primenenie opticheskoi kogerentnoi tomografii v otsenke zadnei kapsuly khrustalika na fone provedeniya antiangiogennoi terapii.

Intravitreal injection (IVI) of anti-angiogenic drugs is one of the most common therapeutic procedures in ophthalmology. In recent years, a new non-contact study method has been developed - anterior segment optical coherence tomography (AS-OCT), which allows the formation of three-dimensional images of the lens and provides more detailed information about its structure and morphology. PURPOSE: This study uses optical coherence tomography method to analyze the risks of developing changes in the posterior lens capsule in patients after IVI of an anti-angiogenic drug. MATERIAL AND METHODS: The study involved 100 people (14 men and 86 women) with a natural lens and neovascular age-related macular degeneration (nAMD). The average age was 70.57±7.98 years. During the study (12 months), all patients underwent IVI of an anti-angiogenic drug aflibercept in the treat-and-extend (T&E) mode. All subjects were divided into 2 groups: with a total number of IVI less than 10 - group 1 (50 patients), and more than 10 IVI - group 2 (50 patients, of which 49 were included in the study). All patients underwent OCT using the Optopol REVO NX device (Poland) with the Anterior B-scan Wide protocol before inclusion in the study, as well as after 3, 6 and 12 months. RESULTS: It was found that the risk of developing a posterior lens capsule rupture, visualized using OCT, depends on the total number of IVI (correlation coefficient 0.473 p=0.001): the more IVI, the higher the probability that damage to the posterior capsule will occur after the next IVI, and after the 15th injection the risk of developing damage to the posterior capsule increases sharply. CONCLUSION: The astudy analyzed the risk factors for the development of posterior lens capsule damage that can be detected using OCT, and presented three risk groups for the development of rupture (or damage) of the posterior lens capsule depending on the number of intravitreal injections performed.

Associations between Serial Intravitreal Injections and Dry Eye.

PURPOSE: To investigate the effects of serial intravitreal injections (IVIs) on the ocular surface and meibomian glands (MGs) in patients treated with anti-vascular endothelial growth factor (anti-VEGF) for neovascular age-related macular degeneration (nAMD). DESIGN: Retrospective, controlled, observational study. PARTICIPANTS: Patients with nAMD receiving unilateral IVIs with anti-VEGF agents. The fellow eye was used as control. METHODS: Tear film and ocular surface examinations were performed on a single occasion at a minimum of 4 weeks after IVI. A pre-IVI asepsis protocol with povidone-iodine (PVP-I) was applied. MAIN OUTCOME MEASURES: Upper and lower MG loss, tear meniscus height (TMH), bulbar redness (BR) score, noninvasive tear break-up time (NIBUT), tear film osmolarity (TOsm), Schirmer test, corneal staining, fluorescein tear film break-up time (TBUT), meibomian gland expressibility (ME), and meibum quality. RESULTS: Ninety patients with a mean age of 77.5 years (standard deviation [SD], 8.4; range 54-95) were included. The median number of IVIs in treated eyes was 19.5 (range, 2-132). Mean MG loss in the upper eyelid was 19.1% (SD, 11.3) in treated eyes and 25.5% (SD, 14.6) in untreated fellow eyes (P = 0.001). For the lower eyelid, median MG loss was 17.4% (interquartile range [IQR], 9.4-29.9) in treated eyes and 24.5% (IQR, 14.2-35.2) in fellow eyes (P < 0.001). Mean BR was 1.32 (SD, 0.46) in treated eyes versus 1.44 (SD, 0.45) in fellow eyes (P = 0.017). Median TMH was 0.36 mm (IQR, 0.28-0.52) in treated eyes and 0.32 mm (IQR, 0.24-0.49) in fellow eyes (P = 0.02). There were no differences between treated and fellow eyes regarding NIBUT, TOsm, Schirmer test, corneal staining, fluorescein TBUT, ME, or meibum quality. CONCLUSIONS: Repeated IVIs with anti-VEGF with preoperative PVP-I application was associated with reduced MG loss, increased tear volume, and reduced signs of inflammation compared with fellow nontreated eyes in patients with nAMD. This regimen may thus have a beneficial effect on the ocular surface. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Membranoproliferative glomerulonephritis after intravitreal vascular growth factor inhibitor injections: A case report and review of the literature.

Systemic administration of agents that inhibit vascular endothelial growth factor (VEGF) and therefore vascular proliferation is often used to treat various cancers. However, these agents are associated with a number of side effects, including proteinuria and renal injury. Intravitreal injection of anti-VEGF agents has become the cornerstone of macular disease treatment. Since these agents cross the blood-retina barrier and enter the circulation, systemic side effects have been reported. We report the novel case of a 57-year-old patient who presented with macular oedema secondary to central retinal vein occlusion, underwent three monthly loading-dose injections with the anti-VEGF agent ranibizumab, and 2 weeks after the second injection presented with biopsy-verified membranoproliferative glomerulonephritis. Twelve weeks after presenting with renal failure and 10 weeks after his last anti-VEGF injection, the patient demonstrated spontaneous recovery of his kidney function. The patient had a history that promoted renal fragility, including hypertension, liver transplantation 6 years earlier for alcohol-related cirrhosis and new-onset diabetes mellitus after transplant. Our literature review and case suggest that although adverse renal events after intravitreal anti-VEGF injections are very rare, ophthalmologists and nephrologists should be aware of this risk.

Topical antibiotic prophylaxis before intravitreal injections: a pilot study.

PURPOSE: To explore whether topical antibiotic prophylaxis in patients scheduled for intravitreal injections achieves surface sterility in a greater proportion of subjects as compared to povidone-iodine alone. MATERIAL AND METHODS: A randomized, triple-blind clinical trial. POPULATION: patients scheduled for intravitreal injections for maculopathy. INCLUSION CRITERIA: any sex and race, age 18 years and above. Subjects were randomized into 4 groups: the first group applied chloramphenicol (CHLORAM), the second netilmicin (NETILM), the third a commercial ozonized antiseptic solution (OZONE), and the fourth applied no drops (CONTROL). OUTCOME VARIABLE: percentage of non-sterile conjunctival swabs. Specimens were collected before and after the application of 5% povidone-iodine moments before the injection. RESULTS: Ninety-eight subjects (33.7% females, 64.3% males), mean age: 70.2 ± 9.3 years (54-91). Before povidone-iodine, both the CHLORAM and NETILM group showed a lower percentage of non-sterile swabs (61.1% and 31.3% respectively), as compared to the OZONE (83.3%) and CONTROL (86.5%) groups (p < .04). However, this statistical difference was lost after the application of povidone-iodine for 3 min. Percentage of non-sterile swabs in each group after applying 5% povidone-iodine: CHLORAM 11.1%, NETILM 12.5%, CONTROL 15.4%, OZONE 25.0%. This was not statistically significant (p > .05). CONCLUSIONS: Topical antibiotic prophylaxis with chloramphenicol or netilmicin drops decreases the bacterial load on the conjunctiva. However, after the application of povidone-iodine, all groups showed a significant reduction in the percentage of non-sterile swabs, and this value was comparable among all groups. For this reason, authors conclude that povidone-iodine alone is sufficient and prior topical antibiotic prophylaxis is not indicated.

Final 4-year results of the RAINBOW real-world study: intravitreal aflibercept dosing regimens in France in treatment-naïve patients with neovascular age-related macular degeneration.

PURPOSE: The purpose of this study is to evaluate real-world treatment outcomes in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept (IVT-AFL) in routine clinical practice in France. METHODS: RAINBOW (NCT02279537) was an ambispective, observational, 4-year study assessing IVT-AFL effectiveness, treatment patterns, and safety in patients with nAMD in France. Treatment-naïve patients prescribed IVT-AFL and treated according to local practice (pro re nata or treat-and-extend) were eligible. Three treatment cohorts were retrospectively identified based on their treatment pattern within the first 12 months: regular (3 initial monthly IVT-AFL injections received within 45-90 days after the first injection in month 0 and followed by injections every 2 months), irregular with the initial monthly injections, and irregular without the initial monthly injections. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline to month 12. The 48-month results are described here. RESULTS: Overall, the study included 516 patients (each with one study eye), and 30.2% of patients completed 48 months of IVT-AFL treatment. Mean change in BCVA from baseline (56.5 letters) to month 48 for patients with an assessment at both time points was + 1.1 (regular cohort, n = 47), + 0.1 (irregular cohort with initial monthly injections, n = 115), and - 1.3 letters (irregular cohort without initial monthly injections, n = 26), representing a decrease from the gains achieved at month 12. Mean number of IVT-AFL injections received by month 48 in the treatment cohorts was 14.9, 13.7, and 11.9, respectively. The safety profile of IVT-AFL was consistent with previous studies. CONCLUSION: In RAINBOW, the 48-month results demonstrate a lack of long-term effectiveness of IVT-AFL treatment of nAMD due to progressive undertreatment in routine clinical practice in France. These real-world findings highlight the importance of 3 initial monthly IVT-AFL injections followed by continuous proactive treatment beyond the first year to achieve optimal functional outcomes. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT02279537.

Delaying anti-VEGF therapy during the COVID-19 pandemic: long-term impact on visual outcomes in patients with neovascular age-related macular degeneration.

OBJECTIVES: To evaluate the outcomes of delayed intravitreal injections (IVIs) caused by the outbreak of coronavirus disease 2019 (COVID-19), in patients with neovascular age-related macular degeneration (nAMD). METHODS: nAMD patients with scheduled IVIs between March 1st and April 30th, 2020 were stratified through a risk-based selection into a non-adherent group (NA-group) if they skipped at least one IVI and an adherent group (A-group) if they followed their treatment schedule. During the pandemic visit (v0), if a significant worsening of the disease was detected, a rescue therapy of three-monthly IVIs was performed. Multimodal imaging and best-corrected visual acuity (BCVA) findings were evaluated after 6 months (v6), compared between groups and with the visit prior the lockdown (v-1). RESULTS: Two hundred fifteen patients (132 females, mean age: 81.89 ± 5.98 years) delayed their scheduled IVI while 83 (53 females, mean age: 77.92 ± 6.06 years) adhered to their protocol. For both groups, BCVA at v0 was significantly worse than v-1 (mean 4.15 ± 7.24 ETDRS letters reduction for the NA-group and 3 ± 7.96 for the A-group) but remained stable at v6. The two groups did not significantly differ in BCVA trends after 6 months and neither for development of atrophy nor fibrosis. CONCLUSIONS: A risk-based selection strategy and a rescue therapy may limit the long-term outcomes of an interruption of the treatment protocol in patients with nAMD.

Posterior Capsular Rupture during Cataract Surgery in Eyes Previously Treated with Intravitreal Injections.

INTRODUCTION: Intravitreal injections (IVIs) are currently the most common intraocular surgical procedure worldwide. Some studies have reported a higher risk of intraoperative complications, namely, posterior capsular rupture (PCR), during cataract surgery. The aim of this retrospective and observational study, conducted at Department of Ophthalmology, Centro Hospitalar Universitário do Porto, was to assess the risk of PCR during cataract surgery in eyes previously treated with IVIs with anti-vascular endothelial growth factor (anti-VEGF) and/or corticosteroids. METHODS: Eyes undergoing cataract surgery between June 2019 and May 2021 were included. Combined surgeries, such as glaucoma surgery and pars plana vitrectomy, were excluded. The occurrence of PCR during cataract surgery in treated and previously untreated eyes with IVI was analyzed. RESULTS: A total of 5,813 cataract surgeries were analyzed; 4.1% of the cases had previously undergone IVI. The PCR rate in cataract surgery was 1.8%: 6.7% in eyes previously treated with IVI and 1.6% without previous IVI (OR = 4.5, 95% CI: 2.6-7.7, p < 0.001). The combined therapy (anti-VEGF with corticosteroids) presents a higher risk compared to the two therapies alone as monotherapy (OR = 11.6, 95% CI: 4.7-28.5, p < 0.001), as well as treated eyes treated with ≥10 IVI (OR = 2.1, 95% CI: 0.8-6.1, p = 0.144) and a time interval between the last IVI and cataract surgery was ≤6 months (OR = 1.9, 95% CI: 0.6-6.1, p = 0.296). CONCLUSION: These results demonstrate that eyes that require IV treatment prior to cataract surgery are at increased risk of CPA during cataract surgery, and careful assessment of the characteristics of the cataract and posterior capsule is critical.

Salvageable waste associated with intravitreal injections: A local medical waste management approach.

BACKGROUND: Healthcare waste management is a globally challenging issue with an increased prevalence of disposable, single-use materials in developed countries and a rapidly ageing population continuing to drive an increase in the use of medical resources. One manifestation of this within ophthalmology is the increasing number of intravitreal injections given for conditions such as age-related macular degeneration and diabetic macular oedema. METHODS: A prospective controlled cohort study was performed over 5 weeks in 2021 during which two sites were selected to compare different approaches to sorting the waste generated by intravitreal injections. At Site A all waste associated with these injections was placed in standard hospital waste bins. Site B was the intervention arm where a real-time sorting of waste occurred. The number of injections given and waste amounts were recorded. RESULTS: 116 and 286 injections were given at Sites A and B, respectively over the study period. Site A generated an average of 470.7 g of waste per injection compared with 175.1 g at our intervention site. This represents a 62.8% reduction (p < 0.001). At Site B, where waste was sorted, a total of 50.1 kg of medical waste was generated from these injections during the study period of which 33.8 kg (67.5%) was salvageable. CONCLUSIONS: This is the first quantification of the medical waste associated with intravitreal injections, a burgeoning treatment for macular degeneration and diabetic retinopathy among other conditions. This study demonstrates a significant reduction in the amount of medical waste produced using an easily implementable real-world methodology.

[Modern trends in anti-VEGF therapy for age-related macular degeneration]. / Sovremennye tendentsii anti-VEGF -terapii vozrastnoi makulyarnoi degeneratsii.

Age-related macular degeneration (AMD) develops in people aged 50 years and older, its pathogenesis involves progressive destruction of the retinal pigment epithelium and Bruch's membrane. There are eight currently known anti-VEGF drugs for treating the neovascular form of AMD, four of them have already been registered and are used in clinical practice. The first registered drug was pegaptanib, which selectively blocks VEGF165. Subsequently, a molecule with a similar mechanism of action was developed and named ranibizumab, which is a humanized monoclonal Fab fragment; it was specifically designed for ophthalmology. Its advantage over pegaptanib was neutralization of all active VEGF-A isoforms. Aflibercept and conbercept are recombinant fusion proteins that act as soluble decoy receptors for VEGF family proteins. Phase III data from the VIEW 1 and 2 studies showed that intraocular injections (IVI) of aflibercept every 1 or 2 months for a year resulted in comparable functional outcomes to monthly IVI of ranibizumab for one year. The next molecule for anti-VEGF therapy that showed effectiveness was brolucizumab - a single-chain fragment of a humanized antibody that binds with high affinity to various VEGF-A isoforms. Simultaneously with studying brolucizumab, another study was conducted involving Abicipar pegol, but that drug showed a high rate of complications. The latest drug registered for the treatment of neovascular AMD is faricimab. The molecule of this drug is a humanized immunoglobulin G antibody that acts on two key points of angiogenesis: VEGF-A and angiopoietin-2 (Ang-2). Thus, the strategy for advancing anti-VEGF therapy lies in the development of molecules with greater efficiency (better effect on newly formed vessels leading to resorption of exudate in the retina, under the neuroepithelium and under the retinal pigment epithelium), which allows not just to preserve vision, but to also significantly improve it when there is no macular atrophy.

Impact of the COVID-19 pandemic's first wave on the care and treatment situation of intravitreal injections in a German metropolitan region.

PURPOSE: This study aims to evaluate the impact of the first coronavirus 2019 (COVID-19) wave in 2020 on patients scheduled for intravitreal injections (IVI) in a German metropolitan region. METHODS: We performed a multicentre prospective survey and retrospective analysis of the records of patients treated with intravitreal injections during the 20-week period from March to July 2020 in all four hospital eye departments in the city of Hamburg using a questionnaire (on treatment adherence, SarsCoV2-related personal, familial and social data) and treatment data. RESULTS: A total of 1038 patients (2472 IVI, 1231 eyes) and 818 questionnaires were evaluated. Longer duration of therapy, lower visual acuity (VA) of the treated and higher VA of the fellow untreated eye was were associated with a higher probability of visit cancellation. Every additional year of life posed a 2.6% lower risk of noncompliance. A COVID-19 infection in the family environment displayed a 5.5-fold chance of visit cancellation. Patients treated for neovascular age-related macular degeneration (nAMD) had a 36% reduced risk of visit cancellation compared to patients with diabetic macular oedema (DME). CONCLUSION: A long preceding treatment period, low VA of the treated eye, high VA of the untreated eye, COVID-19 in the family and DME were identified as risk factors for IVI visit cancellations during the COVID-19 pandemic. Compliance to treatment might be improved in the future by taking these risk factors into account when scheduling patients for IVI during the exceptional circumstances of a pandemic.

PERSEUS-IT 24-month analysis: a prospective observational study to assess the effectiveness of intravitreal aflibercept in routine clinical practice in Italy in patients with neovascular age-related macular degeneration.

PURPOSE: PERSEUS-IT (NCT02289924) was a prospective, observational, 2-year study evaluating the effectiveness and treatment patterns of intravitreal aflibercept (IVT-AFL) in patients with neovascular age-related macular degeneration (nAMD) in routine clinical practice in Italy. METHODS: Treatment-naïve patients with nAMD receiving IVT-AFL per routine clinical practice were enrolled. The primary endpoint was mean change in visual acuity (VA; decimals) from baseline to month (M) 12 and M24. Outcomes were evaluated for the overall study population and independently for the 2 treatment cohorts: regular (3 initial monthly doses, ≥ 7 injections by M12, and ≥ 4 injections between M12 and M24) and irregular (any other pattern). RESULTS: Of 813 patients enrolled, 709 were included in the full analysis set (FAS); VA assessments were available for 342 patients at M12 (FAS1Y, 140 regular and 202 irregular) and 233 patients at M24 (FAS2Y, 37 regular and 196 irregular). In the overall FAS, the mean ± SD change in VA from baseline to M12 and M24 was + 0.09 ± 0.24 and + 0.02 ± 0.25 decimals, and there was a statistically significant difference between the regular and irregular cohorts in both FAS1Y (p = 0.0034) and FAS2Y (p = 0.0222). Ocular treatment-emergent adverse events were reported in 4.1% (n = 33/810 [safety set]) of patients. CONCLUSION: In PERSEUS-IT, clinically relevant functional and anatomic improvements were observed within the first 12 months of IVT-AFL treatment in routine clinical practice in Italy in patients with treatment-naïve nAMD. These gains were generally maintained across the 2-year study. The safety profile of IVT-AFL was consistent with prior studies. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT02289924. DATE OF REGISTRATION: November 13, 2014.

Prevalence and implications of the presence of intraocular silicone oil droplets in patients treated with intravitreal injections of anti-VEGF.

BACKGROUND: To determine the percentage of patients who have silicone droplets in the vitreous after treatment with different anti-Vascular Endothelial Growth Factor (anti-VEGF) intravitreal injections (IVI) and how symptomatic they are. METHODS: One hundred fifty-two eyes of 140 patients who had at least received an IVI were recruited for this study. Data collection included the number and type of IVI (aflibercept, ranibizumab and bevacizumab) and the follow-up time. A complete ophthalmologic examination was carried out and patients were classified in four groups according to the amount of silicone droplets found in dilated fundoscopy (nonexistent, scarce, moderate and abundant). Measurement of intraocular pressure (IOP) was also carried out. An interview was conducted to report the presence and intensity of the symptomatology. RESULTS: Silicone oil droplets were reported in 109 eyes (71.7%). A positive correlation was found between the number of IVIs received and the quantity of droplets found, especially when aflibercept was used. Posterior vitreous detachment (PVD) was present in 65.8% of the patients, showing a positive correlation with the number of bubbles. Regarding the symptomatology, 60 eyes (39.5%) had floaters and the disturbance was reported to be 4 out of 10. The group with a moderate amount of silicone droplets had the highest percentage of floaters (60%). No statistical differences in the IOP were found between groups, although the group with abundant droplets had a higher mean IOP. CONCLUSION: A high prevalence of silicone droplets in vitreous of patients who undergo IVI treatment was found. It appears to have little impact on symptomatology and rise of IOP.

Renal thrombotic microangiopathy and nephrotic proteinuria induced by intravitreal injection of aflibercept for diabetic macular edema.

BACKGROUND: Vascular endothelial growth factor inhibitors (VEGFIs) are used to treat malignant neoplasms and ocular diseases by inhibiting angiogenesis. Systemic use of VEGFIs has various side effects, including hypertension, proteinuria, and thrombotic microangiopathy, but adverse events due to intravitreal injection of VEGFIs have not been fully clarified. Although age-related macular degeneration was initially the most common target of intravitreal injection of VEGFIs, it has also been applied sporadically for diabetic macular edema in recent years. Proteinuria following intravitreal injection of VEGFIs would be reversible. In patients with diabetes mellitus (DM), however, it would be difficult to determine whether kidney damage arises from the clinical course of DM or from intravitreal injection of VEGFIs for diabetic macular edema. CASE PRESENTATION: A 55-year-old woman with a 20-year history of type 2 DM began intravitreal injection of VEGFI (aflibercept, 2 mg every 4 weeks) for treatment of diabetic macular edema 2 years previously. She presented with leg edema, hypertension, and nephrotic-range proteinuria 14 months after the first injection. Histological examination of renal biopsy specimens revealed diabetic nephropathy with renal thrombotic microangiopathy probably associated with intravitreal injection of VEGFI. The patient's nephrotic syndrome completely improved at 6 months after simply discontinuing aflibercept. CONCLUSIONS: This is a precious report of pathologically investigated renal thrombotic microangiopathy leading to nephrotic syndrome due to intravitreal injection of aflibercept for diabetic macular edema in a patient with type 2 DM. Renal function and proteinuria should be monitored in diabetic patients who receive intravitreal injection of a VEGFI. If kidney damage develops independent of the clinical course of DM during intravitreal injection of a VEGFI, renal biopsy should be performed and intravitreal VEGFI injection discontinued.

Closure of Full-Thickness Macular Holes Associated with Macular Edema with Medical Therapy.

PURPOSE: The purpose of this study was to report the closure of macular hole without surgery in 7 cases using medical therapies. METHODS: The retrospective review of 7 cases of full-thickness macular holes, which closed after medical therapy without surgery. RESULTS: Seven eyes of 7 patients developed full-thickness macular holes, which initially closed on medical therapy without surgery. Six patients were kept on maintenance therapy; 1 recurred and 5 did not develop recurrence. One patient was taken off of maintenance therapy and later developed recurrent macular hole requiring macular hole surgery. CONCLUSIONS: Medical therapy to decrease macular edema may facilitate macular hole closure and should be considered, especially for small macular holes with significant edema. Reopening of macular holes may occur after stopping topical maintenance therapy for macular edema, which occurred at 10 weeks and 9 months after maintenance therapy was discontinued or markedly tapered.

New Insights into Treating Early and Advanced Stage Diabetic Retinopathy.

Diabetic retinopathy (DR) is the leading cause of preventable blindness in the working-age population. The disease progresses slowly, and we can roughly differentiate two stages: early-stage (ESDR), in which there are mild retinal lesions and visual acuity is generally preserved, and advanced-stage (ASDR), in which the structural lesions are significant and visual acuity is compromised. At present, there are no specific treatments for ESDR and the current recommended action is to optimize metabolic control and maintain close control of blood pressure. However, in the coming years, it is foreseeable that therapeutic strategies based in neuroprotection will be introduced in the clinical arena. This means that screening aimed at identifying patients in whom neuroprotective treatment might be beneficial will be crucial. Regarding the treatment of ASDR, the current primary course is based on laser photocoagulation and intravitreal injections of anti-angiogenic factors or corticosteroids. Repeated intravitreal injections of anti-VEGF agents as the first-line treatment would be replaced by more cost-effective and personalized treatments based on the results of "liquid biopsies" of aqueous humor. Finally, topical administration (i.e., eye drops) of neuroprotective, anti-inflammatory and anti-angiogenic agents will represent a revolution in the treatment of DR in the coming decade. In this article, all these approaches and others will be critically discussed from a holistic perspective.

Changes of Estimated Glomerular Filtration Rate and Glycated Hemoglobin A1c in Diabetic Macular Edema Patients Treated by Ranibizumab and Aflibercept in the Tertiary Referral Hospital.

Background and Objectives: Intravitreal injections (IVI) of vascular endothelial growth factor (VEGF) inhibitors are guideline-indicated treatments for diabetic macular edema (DME). However, some recent data have suggested that IVI VEGF inhibitors might, through systemic absorption, lead to a reduction in renal function. Our study aims to compare changes in glycated hemoglobin A1c (HbA1c) and estimated glomerular filtration rate (eGFR) between patients who received IVI ranibizumab and aflibercept treatment and patients who have not received IVI treatments. Materials and Methods: There were 17,165 DME patients with documented ophthalmology visits in the China Medical University Hospital-Clinical Research Data Repository. Those with a history of ESRD or bevacizumab treatment history, and those with missing information on HbA1c or eGFR, were excluded. After matching by age (±2 years), gender, and the year of clinical visit, 154 patients with medical treatment (including ranibizumab and aflibercept) and 154 patients without medical treatment were included in the study. The difference between HbA1c and eGFR at baseline and 3 and 12 months after the index date between the two groups was assessed. Results: Mean HbA1c and eGFR decreased between baseline and 12 months after the index date in both groups (p < 0.05). Compared with the non-treatment group, the treatment group had significantly lower HbA1c 3 and 12 months after the index date. There was no significant difference in eGFR between the two groups. In the generalized estimating equations (GEE) model, HbA1c in the treatment group was lower than the non-treatment group (−0.44%, 95% CI = −0.75, −0.14), but eGFR was similar after adjusting for age, gender, and index-year. HbA1c and eGFR decreased with the time in the adjusted GEE model (p < 0.0001) in both groups. Conclusions: This study showed that eGFR decreased with age and time and was not related to IVI anti-VEGF treatments in our tertiary referral hospital. IVI anti-VEGF therapy was also associated with better HbA1c control. It is suggested that DME patients can receive intravitreal VEGF inhibitors without inducing more renal impairment.

Smart AMD prognosis through cellphone: an innovative localized AI-based prediction system for anti-VEGF treatment prognosis in nonagenarians and centenarians.

BACKGROUND AND OBJECTIVE: Age-related macular degeneration (AMD) is one of the most common reasons for blindness in the world today. The most common treatment for wet AMD is the intravitreal injections for inhibiting vascular-endothelial-derived growth factor (VEGF). This treatment usually involves multiple injections and thus multiple clinic visits, which not only causes increased cost on national health services but also causes exposure to the hospital environment, which is sometimes high risk considering current COVID crisis. The treatment, in spite of the above concerns, is usually effective. However, in some cases, either the medicine fails to produce the anticipated favourable outcome, resulting in waste of time, medication, efforts, and above all, psychological distress to the patients. Hence, early predictability of anatomical as well as functional effectiveness of the treatment appears to be a very desirable capability to have. METHOD: A machine learning approach using adaptive neuro-fuzzy inference system (ANFIS) of two-sample prediction model has been presented that requires only the baseline measurements and changes in visual acuity (VA) as well as macular thickness (MAC) after four months of treatment to estimate the values of VA and MAC at 8 and 12 months. In contrast to most of the AI techniques, ANFIS approach has shown the capability of the algorithm to work with very small dataset as well, which makes it a perfect candidate for the presented solution. RESULTS: The presented model has shown to have a very high accuracy (> 92%) and works in near-real-time scenarios. It has been converted into a smart phone App, OphnosisAMD, for convenient usage. With this App, the clinician can visualize the progression of the patient for a specific treatment and can decide on continuing or changing the treatment accordingly. The complete AI engine developed with the ANFIS algorithm is localized to the phone through the App, implying that there is no need for internet or cloud connectivity for this App to function. This makes it ideal for remote usage, especially under the current COVID scenarios. CONCLUSIONS: With a smart AI-based App on their fingertips, the presented system provides ample opportunity to the doctors to make a better decision based on the estimated progression, if the same drug is continued with (good/fair prognosis) or alternate treatment should be sought (bad prognosis). From a functional point of view, a prediction algorithm is triggered through simple entry of the relevant parameters (baseline and 4 months only). No internet/cloud connectivity is needed since the algorithm and the trained network are fully embedded in the App locally. Hence, using the App in remote and/or non-connected isolated areas is possible, especially in the secluded patients during the COVID scenarios.