Efficacy and Safety of Brolucizumab for Diabetic Macular Edema: The KINGFISHER Randomized Clinical Trial.

Importance: Despite the effectiveness of existing anti-vascular endothelial growth factor (VEGF) therapies, a need remains for further treatment options to improve response rates and/or reduce injection or monitoring frequency in patients with diabetic macular edema (DME). Objective: To evaluate the efficacy and safety of brolucizumab vs aflibercept dosed every 4 weeks in participants with DME. Design, Participants, and Setting: This 52-week, double-masked, phase 3 randomized clinical trial included treatment-naive adults and adults who had previously received anti-VEGF therapy. Data were collected from September 2019 to March 2020, and data were analyzed from April 2020 to February 2021. Intervention: Brolucizumab, 6 mg, intravitreal injection every 4 weeks or aflibercept, 2 mg, intravitreal injection every 4 weeks. Main Outcomes and Measures: Participants were randomized 2:1 to brolucizumab, 6 mg, or aflibercept, 2 mg. The primary end point was change from baseline in best-corrected visual acuity at week 52. Secondary end points were the proportion of participants with a 2-step improvement or greater from baseline in Diabetic Retinopathy Severity Scale score, the proportion of eyes with absence of both subretinal fluid and intraretinal fluid, change from baseline in central subfield thickness, and safety at week 52. Results: A total of 517 participants were randomized to brolucizumab (n = 346) or aflibercept (n = 171); 299 (57.8%) were male, and the mean (SD) age was 60.7 (10.2) years. Brolucizumab was noninferior to aflibercept in best-corrected visual acuity (Early Treatment Diabetic Retinopathy Study letter score) change from baseline at week 52 (brolucizumab, 12.2-letter improvement; aflibercept, 11.0-letter improvement; difference, 1.1; 95% CI, -0.6 to 2.9; noninferiority margin, 4; P < .001). Brolucizumab was superior to aflibercept for the proportion of eyes without subretinal and intraretinal fluid (brolucizumab, 144 of 346 [41.6%]; aflibercept, 38 of 171 [22.2%]; difference, 20.0%; 95% CI, 12.5to 28.6; P < .001) and mean central subfield thickness change from baseline at week 52 (brolucizumab, -237.8 µm; aflibercept, -196.5 µm; difference, -41.4; 95% CI, -58.9 to -23.8; P < .001). Incidence of intraocular inflammation was 4.0% (14 of 346) in the brolucizumab arm and 2.9% (5 of 171) in the aflibercept arm, incidence of retinal vasculitis was 0.9% (3 of 346) and 0.6% (1 of 171), respectively, and incidence of retinal vascular occlusion was 0.3% (1 of 346) and 0.6% (1 of 171). One participant in the brolucizumab arm had retinal artery occlusion. Conclusions and Relevance: In these study participants with DME, no clinically meaningful differences in visual outcomes were noted between the brolucizumab and aflibercept arms; some superior anatomic improvements were noted in the brolucizumab arm. No new safety concerns were identified. Trial Registration: ClinicalTrials.gov Identifier: NCT03917472.

Efficacy and safety of avacincaptad pegol in patients with geographic atrophy (GATHER2): 12-month results from a randomised, double-masked, phase 3 trial.

BACKGROUND: Geographic atrophy is an advanced form of dry age-related macular degeneration that can lead to irreversible vision loss and high burden of disease. We aimed to assess efficacy and safety of avacincaptad pegol 2 mg in reducing geographic atrophy lesion growth. METHODS: GATHER2 is a randomised, double-masked, sham-controlled, 24-month, phase 3 trial across 205 retina clinics, research hospitals, and academic institutions globally. To be eligible, patients had to be aged 50 years or older with non-centrepoint-involving geographic atrophy and best corrected visual acuity between 20/25 and 20/320 in the study eye. Eligible patients were randomly assigned (1:1) to monthly avacincaptad pegol 2 mg administered as a 100 µL intravitreal injection or sham for the first 12 months. Randomisation was performed using an interactive response technology system with stratification by factors known to be of prognostic importance in age-related macular degeneration. Patients, investigators, study centre staff, sponsor personnel, and data analysts were masked to treatment allocation. The primary endpoint was geographic atrophy lesion size measured by fundus autofluorescence at baseline, month 6, and month 12. Efficacy and safety analyses were done in the modified intention-to-treat and safety populations, respectively. This trial is registered with ClinicalTrials.gov, NCT04435366. FINDINGS: Between June 22, 2020, and July 23, 2021, 1422 patients were screened for eligibility, of whom 448 were enrolled and randomly assigned to avacincaptad pegol 2 mg (n=225) or sham (n=223). One patient in the sham group did not receive study treatment and was excluded from analyses. There were 154 (68%) female patients and 71 (32%) male patients in the avacincaptad pegol 2 mg group, and 156 (70%) female patients and 66 (30%) male patients in the sham group. From baseline to month 12, the mean rate of square-root-transformed geographic atrophy area growth was 0·336 mm/year (SE 0·032) with avacincaptad pegol 2 mg and 0·392 mm/year (0·033) with sham, a difference in growth of 0·056 mm/year (95% CI 0·016-0·096; p=0·0064), representing a 14% difference between the avacincaptad pegol 2 mg group and the sham group. Ocular treatment-emergent adverse events in the study eye occurred in 110 (49%) patients in the avacincaptad pegol 2 mg group and 83 (37%) in the sham group. There were no endophthalmitis, intraocular inflammation, or ischaemic optic neuropathy events over 12 months. To month 12, macular neovascularisation in the study eye occurred in 15 (7%) patients in the avacincaptad pegol 2 mg group and nine (4%) in the sham group, with exudative macular neovascularisation occurring in 11 (5%) in the avacincaptad pegol 2 mg group and seven (3%) in the sham group. INTERPRETATION: Monthly avacincaptad pegol 2 mg was well tolerated and showed significantly slower geographic atrophy growth over 12 months than sham treatment, suggesting that avacincaptad pegol might slow disease progression and potentially change the trajectory of disease for patients with geographic atrophy. FUNDING: Iveric Bio, An Astellas Company.

Biosimilars in the Treatment of Retinal Disease in the United States.

Biosimilars have recently emerged into the vitreoretinal pharmaceutical market. This review defines biosimilars, discusses the approval process, and reviews the benefits, risks, and controversies regarding biosimilars. This review also discusses ranibizumab biosimilars that have recently received United States Food and Drug Administration approval in the United States and discusses anti-vascular endothelial growth factor biosimilars that are in development. [Ophthalmic Surg Lasers Imaging Retina 2023;54:362-366.].

Bilateral Hypotony Maculopathy Associated With Ipilimumab and Nivolumab Therapy Unresponsive to Corticosteroid Treatment.

In rare instances, immunotherapy associated with hypotony and uveitis has been documented. We report the case of a 72-year-old man treated with 2 months of ipilimumab and nivolumab for metastatic melanoma who developed bilateral hypotony maculopathy and serous choroidal detachments without prominent initial uveitis. Despite treatment with topical, periocular, and intraocular corticosteroid injection, hypotony persisted 18 months after immunotherapy cessation. The patient's unresponsiveness to corticosteroids indicates the need to further explore the mechanism behind immune checkpoint inhibitor-associated hypotony. We hypothesize that immunotherapy significantly decreased aqueous humor production through ciliary body inflammation, disruption, or shutdown. [Ophthalmic Surg Lasers Imaging Retina 2023;54:301-304.].

The 0.19-mg Fluocinolone Acetonide Implant for the Treatment of Diabetic Macular Edema: An Expert Consensus.

BACKGROUND AND OBJECTIVE: To better understand the level of agreement among retina specialists on the role of inflammation in diabetic retinopathy (DR) and diabetic macular edema (DME), and the use of 0.19-mg fluocinolone acetonide (FAc) implant in DME treatment, a consensus survey was drafted and disseminated to retina specialists across the United States. MATERIALS AND METHODS: Using the modified Delphi method, a list of 12 consensus statements were generated by the coauthors based on short-answer responses to an initial survey. In total, 56 retina specialists completed the entire consensus survey. Except for two multiple-choice questions, there were 10 consensus statements that used a modified Likert scale to indicate their level of agreement to the statement: Agree = 3, Mostly Agree = 2, Mostly Disagree = 1, Disagree = 0. Percentage agreement and 95% confidence intervals (CIs) were calculated, and a consensus threshold was set at > 80% agreement for each statement. RESULTS: Seven of 10 consensus statements using the modified Likert scale reached consensus, including those on the role of inflammation in pathophysiology of DR/DME, injection burden and patient adherence, and efficacy and safety of the FAc implant. The remaining three statements displayed high agreement with average scores > 80%, but the 95% CIs were below threshold. These included the impact of the FAc implant on DR progression, FAc as baseline therapy for DME, and the effectiveness of the steroid challenge to mitigate intraocular pressure risk after FAc use. Two multiple-choice questions focused on clinical situations in which corticosteroids would be used as baseline therapy for DME (pseudophakic eye [73%], recent stroke/myocardial infarction [66%], and pregnancy/breastfeeding [66%]) and which delivery route satisfies the steroid challenge for the FAc implant (intravitreal [100%], sub-tenon/periocular [73%], and topical [57%]). CONCLUSIONS: Physicians highly agreed on the role of inflammation in pathophysiology of DR/DME, injection burden and patient adherence, and efficacy and safety of the FAc implant. However, full consensus was not found on the impact of the FAc implant on DR progression, FAc as baseline therapy for DME, and the effectiveness of the steroid challenge to mitigate intraocular pressure risk after FAc use. [Ophthalmic Surg Lasers Imaging Retina. 2023;54(3):166-173.].

Ranibizumab port delivery system: a clinical perspective.

Age-related macular degeneration (AMD) represents a leading cause of blindness worldwide. Neovascular AMD (nAMD) is a subtype of AMD most frequently treated with intravitreal anti-vascular endothelial growth factor (aVEGF) injections, which has allowed for patients to maintain vision that would have otherwise been lost. However, the need for frequent intravitreal injections for optimal results poses a risk for undertreatment in nAMD patients due to the high treatment burden associated with current aVEGF therapy. Many novel agents and pathways are being explored and targeted for less burdensome treatment options, one of which is the ranibizumab port delivery system (PDS). The PDS is a surgically implanted, refillable device that allows for the sustained release of ranibizumab, a widely used aVEGF agent, into the vitreous cavity. Positive results non-inferior to monthly ranibizumab injections in both phase II and phase III clinical trials allowed for FDA approval of the device with refill intervals of 6 months, which represents the longest approved treatment interval to date for nAMD therapy. This article reviews the need for a durable nAMD treatment option in real-world practice, the clinical trial and extension study data for the PDS, the risk of adverse events and safety profile of the PDS and the potential clinical role of the PDS in answering the real-world needs of nAMD treatment. In addition, other pipeline sustained-treatment modalities are discussed in the context of ongoing clinical trials.

Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): two randomised, double-masked, phase 3 trials.

BACKGROUND: To reduce treatment burden and optimise patient outcomes in diabetic macular oedema, we present 1-year results from two phase 3 trials of faricimab, a novel angiopoietin-2 and vascular endothelial growth factor-A bispecific antibody. METHODS: YOSEMITE and RHINE were randomised, double-masked, non-inferiority trials across 353 sites worldwide. Adults with vision loss due to centre-involving diabetic macular oedema were randomly assigned (1:1:1) to intravitreal faricimab 6·0 mg every 8 weeks, faricimab 6·0 mg per personalised treatment interval (PTI), or aflibercept 2·0 mg every 8 weeks up to week 100. PTI dosing intervals were extended, maintained, or reduced (every 4 weeks up to every 16 weeks) based on disease activity at active dosing visits. The primary endpoint was mean change in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Efficacy analyses included the intention-to-treat population (non-inferiority margin 4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters); safety analyses included patients with at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (YOSEMITE NCT03622580 and RHINE NCT03622593). FINDINGS: 3247 patients were screened for eligibility in YOSEMITE (n=1532) and RHINE (n=1715). After exclusions, 940 patients were enrolled into YOSEMITE between Sept 5, 2018, and Sept 19, 2019, and 951 patients were enrolled into RHINE between Oct 9, 2018, and Sept 20, 2019. These 1891 patients were randomly assigned to faricimab every 8 weeks (YOSEMITE n=315, RHINE n=317), faricimab PTI (n=313, n=319), or aflibercept every 8 weeks (n=312, n=315). Non-inferiority for the primary endpoint was achieved with faricimab every 8 weeks (adjusted mean vs aflibercept every 8 weeks in YOSEMITE 10·7 ETDRS letters [97·52% CI 9·4 to 12·0] vs 10·9 ETDRS letters [9·6 to 12·2], difference -0·2 ETDRS letters [-2·0 to 1·6]; RHINE 11·8 ETDRS letters [10·6 to 13·0] vs 10·3 ETDRS letters [9·1 to 11·4] letters, difference 1·5 ETDRS letters [-0·1 to 3·2]) and faricimab PTI (YOSEMITE 11·6 ETDRS letters [10·3 to 12·9], difference 0·7 ETDRS letters [-1·1 to 2·5]; RHINE 10·8 ETDRS letters [9·6 to 11·9], difference 0·5 ETDRS letters [-1·1 to 2·1]). Incidence of ocular adverse events was comparable between faricimab every 8 weeks (YOSEMITE n=98 [31%], RHINE n=137 [43%]), faricimab PTI (n=106 [34%], n=119 [37%]), and aflibercept every 8 weeks (n=102 [33%], n=113 [36%]). INTERPRETATION: Robust vision gains and anatomical improvements with faricimab were achieved with adjustable dosing up to every 16 weeks, demonstrating the potential for faricimab to extend the durability of treatment for patients with diabetic macular oedema. FUNDING: F Hoffmann-La Roche.

Quantifying burden of intravitreal injections: questionnaire assessment of life impact of treatment by intravitreal injections (QUALITII).

AIM: To quantify the areas of burden experienced by patients requiring repeated intravitreal injections (IVI) in the management of exudative retinal diseases. METHODS: The validated Questionnaire to Assess Life Impact of Treatment by Intravitreal Injections survey was administered to patients at four retina clinical practices across four US states. The primary outcome measure was Treatment Burden Score (TBS), a single score assessing overall burden. RESULTS: Of 1416 (n=657 age-related macular degeneration; n=360 diabetic macular oedema/diabetic retinopathy; n=221 retinal vein occlusion; n=178 other/uncertain) patients, 55% were women with an average age of 70 years. Patients most frequently reported receiving IVI every 4-5 weeks (40%). The mean TBS was 16.1±9.2 (range 1-48; scale of 1-54), and the TBS was higher in patients with diabetic macular oedema and/or diabetic retinopathy (DMO/DR) (17.1) compared with those with age-related macular degeneration (15.5) or retinal venous occlusive (15.3) (p=0.028). Though the mean level of discomfort was quite low (1.86) (scale 0-6), 50% of patients reported experiencing side effects more than half of the visits. Patients having received fewer than 5 IVI reported higher mean anxiety levels before (p=0.026), during (p=0.050) and after (p=0.016) treatment compared with patients having received more than 50 IVI. After the procedure, 42% of patients reported restrictions from usual activities due to discomfort. Patients reported a high mean satisfaction rating of 5.46 (scale 0-6) with the care of their diseases. CONCLUSIONS: The mean TBS was moderate and highest among patients with DMO/DR. Patients with more total injections reported lower levels of discomfort and anxiety but higher disruption to daily life. Despite the challenges related to IVI, the overall satisfaction with treatment remained high.

Angiopoietins as Potential Targets in Management of Retinal Disease.

The Ang/Tie2 pathway complements VEGF-mediated activity in retinal vascular diseases such as DME, AMD, and RVO by decreasing vascular integrity, increasing neovascularization, and increasing inflammatory signaling. Faricimab is a bispecific antibody that has been developed as an inhibitor of both VEGF and Ang2 that has shown positive results in phase I, II and III trials. Recent Year 1 data from phase III clinical trials YOSEMITE, RHINE, TENAYA, and LUCERNE have confirmed the efficacy, safety, durability, and superiority of faricimab in patients with DME and nAMD. Faricimab, if approved, may significantly decrease treatment burden in patients with retinal vascular diseases to a greater extent than would current standard of care anti-VEGF injections.

Real-World Performance of a Self-Operated Home Monitoring System for Early Detection of Neovascular Age-Related Macular Degeneration.

The real-world performance of a home telemonitoring strategy (ForeseeHome AMD Monitoring System®, Notal Vision, Inc.,Manassas VA, USA) was evaluated and compared to the device arm of the AREDS2-HOME study among patients with intermediate AMD (iAMD) who converted to neovascular AMD (nAMD). All patients with confirmed conversion to nAMD who used the home monitoring system from 10/2009 through 9/2018 were identified by Notal Vision Diagnostic Clinic's medical records. Selected outcome variables were evaluated, including visual acuity (VA) at baseline and at conversion, and change in visual acuity (VA) from baseline to time of conversion. In total, 8991 patients performed 3,200,999 tests at a frequency of 5.6 ± 3.2 times/week. The 306 eyes that converted from iAMD to nAMD over the study period (a 2.7% annual rate) were included in the analyses. There was a median (interquartile range) change of -3.0 (0.0-(-10.0)) letters among converted eyes, 81% [95% confidence interval (72-88%)] maintained a VA ≥ 20/40 at the time of conversion, while 69% of the conversion detections were triggered by system alerts. The real-world performance of an at-home testing strategy was similar to that reported for the device arm of the AREDS2-HOME study. The home telemonitoring system can markedly increase early detection of conversion to nAMD.

Early Experience With Brolucizumab Treatment of Neovascular Age-Related Macular Degeneration.

IMPORTANCE: Outcome data are limited regarding early experience with brolucizumab, the most recently approved anti-vascular endothelial growth factor (VEGF) agent for the treatment of neovascular age-related macular degeneration (nAMD). OBJECTIVE: To report clinical outcomes after intravitreous injection (IVI) of brolucizumab, 6 mg, for nAMD. DESIGN, SETTING, AND PARTICIPANTS: This retrospective case series conducted at 15 private or academic ophthalmological centers in the United States included all consecutive patients with eyes treated with brolucizumab by 6 retina specialists between October 17, 2019, and April 1, 2020. EXPOSURES: Treatment with brolucizumab IVI, 6 mg. MAIN OUTCOMES AND MEASURES: Change in mean visual acuity (VA) and optical coherence tomography parameters, including mean central subfield thickness and presence or absence of subretinal and/or intraretinal fluid. Secondary outcomes included ocular and systemic safety. RESULTS: A total of 172 eyes from 152 patients (87 women [57.2%]; mean [SD] age, 80.0 [8.0] years) were included. Most eyes (166 [96.5%]) were not treatment naive, and 65.7% of these eyes (109 of 166) were switched from the prior anti-VEGF agent because of persistent fluid detected on optical coherence tomography scans. Study eyes received a mean (SD) of 1.46 (0.62) brolucizumab IVIs. The mean (SD) VA prior to starting brolucizumab was a 64.1 (15.9) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score (Snellen equivalent, 20/50) and was a 63.3 (17.2) ETDRS letter score (Snellen equivalent, 20/63) at the last study evaluation (mean difference, 0.8; 95% CI, -2.7 to 4.3; P = .65). When analyzed by number of brolucizumab IVIs, the presence or absence of fluid prior to starting brolucizumab, or the presence or absence of intraocular inflammation after receiving brolucizumab, there was no difference in mean VA prior to starting brolucizumab compared with after brolucizumab IVIs or at the final study evaluation. The mean (SD) central subfield thickness in all eyes prior to starting brolucizumab was 296.7 (88.0) µm and was 269.8 (66.5) µm at the last study examination (mean difference, 26.9 µm; 95% CI, 9.0-44.7 µm; P = .003). Intraocular inflammation was reported in 14 eyes (8.1%) and was self-limited and resolved without treatment in almost half those eyes (n = 6). One previously reported eye (0.6%) had occlusive retinal vasculitis and severe loss of vision. CONCLUSIONS AND RELEVANCE: In this analysis of brolucizumab IVI for nAMD, VA remained stable, with a reduction in central subfield thickness. Intraocular inflammation events ranged from mild with spontaneous resolution to severe occlusive retinal vasculitis in 1 eye.

Evolving Guidelines for Intracameral Injection.

PURPOSE: To review evidence and provide guidelines on intracameral (ICM) injection techniques and monitoring. MATERIALS AND METHODS: A review of published literature on ICM injection and intravitreal injections formed the basis for roundtable deliberations by an expert panel of ophthalmologists. RESULTS: ICM injection as a way to deliver medications is growing in popularity. However, there is limited published literature and no standard approach to best practices for ICM injections, particularly when not accompanying another surgical procedure. Fortunately, there is long clinical experience with ICM manipulation and a large body of evidence surrounding intravitreal injections that has provided important guidance. The expert panel formulates several concrete guidelines and many suggested techniques to help physicians safely and effectively employ ICM injections. CONCLUSIONS: This committee addressed the many considerations surrounding ICM injection of drugs or implants and agree that it is a safe and effective surgical procedure when performed with appropriate training and according to established safe practices.

Macular thickness amplitude changes when switching from discontinuous to continuous therapy for diabetic macular oedema.

OBJECTIVE: To investigate if the mean central retinal thickness (CRT) amplitude, measured between visits, is consistently decreased when switching from discontinuous to continuous therapy for diabetic macular oedema (DME) following fluocinolone acetonide (FAc) administration. METHODS AND ANALYSIS: In this retrospective cohort study, all patients with DME treated with FAc at a single centre were included. The primary outcome was CRT amplitude changes measured at each visit prior to and after FAc administration. Secondary outcomes included average number of DME treatments before and after FAc injection, visual acuity and intraocular pressure changes. RESULTS: Nineteen eyes were included. The mean (SD) follow-up after FAc was 399 (222) days. The mean (SD) CRT amplitude before FAc was 194.6 (114.90) µm, and following FAc administration, the amplitude decreased to 70.8 (94.23) µm (95% CI -189.5 to -58.1; p≤0.001). After FAc, the number of treatments required per month significantly decreased from an average of 1 treatment every 2.7 months to every 6 months (p=0.009). CONCLUSION: In patients with DME, the CRT amplitude values and number of treatments significantly decrease following FAc administration while maintaining vision. Further studies are needed to evaluate the significance of these interesting findings.

Current and upcoming anti-VEGF therapies and dosing strategies for the treatment of neovascular AMD: a comparative review.

Age-related macular degeneration is the leading cause of vision loss in the developed world, with the expected number of affected elderly individuals reaching 17.8 million. Antivascular endothelial growth factor (anti-VEGF) injection therapy has been instrumental in treating a disease process that was previously thought to be untreatable. Over the past two decades, landmark studies have demonstrated the efficacy of different anti-VEGF medications and investigated the optimal dosing regimen and delivery mechanism to increase overall vision and minimise patient burden. In this review, we outline landmark neovascular age-related macular degeneration clinical trials that have demonstrated level 1 evidence for its usage or have contributed to the understanding of how to dose these agents.

Monthly Versus Treat-and-Extend Ranibizumab for Diabetic Macular Edema: A Prospective, Randomized Trial.

BACKGROUND AND OBJECTIVE: Compare fixed monthly dosing of ranibizumab to treat-and-extend (T&E) ranibizumab during a period of 24 months for diabetic macular edema (DME) treatment. PATIENTS AND METHODS: Single-center, randomized, prospective pilot study that included 20 eyes of 20 subjects. Patients' best-corrected visual acuity (BCVA) was less than or equal to 20/40 and central foveal thickness on spectral-domain optical coherence tomography was greater than 325 µm. Intravitreal ranibizumab was dosed monthly or by protocol-specified treat-and-extend. Primary outcome was mean change in mean BCVA. Institutional review board approval was obtained. RESULTS: At month 24 (M24), there was a mean 8.3-letter gain in the monthly treatment group and an 8.5-letter gain in the T&E group (P = .082; 90% confidence interval). The average change from baseline BCVA was not statistically significantly different at any timepoint. At M24, the median number of injections in the monthly and T&E groups were 22.5 and 18.5, respectively (P = .287). CONCLUSIONS: Visual acuity with monthly dosing appears equivalent to T&E dosing during the course of 24 months. There was a trend toward a lower injection burden in the T&E arm. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e191-e197.].

When and How to Incorporate Steroids for Persistent Diabetic Macular Edema: A Discussion of Real-World Treatment Optimization Strategies.

In the United States, diabetic macular edema (DME) is the leading cause of vision loss among people with diabetic retinopathy. Despite the availability of different therapies for DME, up to half of patients with DME show some persistent edema after anti-vascular endothelial growth factor (VEGF) treatment alone, leaving these patients at high risk for vision loss. However, dosing in a similar fashion to that of pivotal anti-VEGF trials is difficult because of real-life challenges faced in clinical practice. This is particularly true for DME, in that the frequency and burden of anti-VEGF injections are a major challenge to patient care. Research evaluating anti-VEGF therapies has shaped the treatment paradigms for patients with DME, and similar benefits have also been noted in clinical trials evaluating the use of intravitreal steroids. Treatment with a long-term intravitreal corticosteroid, which requires fewer injections than treatment with most short-acting therapies, has been found to reduce inflammation and improve vision in a percentage of patients. This roundtable discussion, which took place during the 2018 annual meeting of the Vit-Buckle Society, reviews the current treatment paradigms for DME and evaluates how to customize and optimize treatment strategies geared toward individualized patient care. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:S5-S15.].

Ranibizumab Induces Regression of Diabetic Retinopathy in Most Patients at High Risk of Progression to Proliferative Diabetic Retinopathy.

PURPOSE: To evaluate diabetic retinopathy (DR) outcomes with ranibizumab (Lucentis, Genentech, Inc., South San Francisco, CA) treatment in patients with DR and diabetic macular edema (DME) at high risk of progression to proliferative disease. DESIGN: Post hoc analysis of the phase 3 RIDE (ClinicalTrials.gov identifier, NCT00473382) and RISE (ClinicalTrials.gov identifier, NCT00473330) clinical trials of ranibizumab for the treatment of DME. PARTICIPANTS: Seven hundred forty-six patients with baseline fundus photographs and randomized for treatment. METHODS: Diabetic retinopathy outcomes were assessed through month 36 by baseline DR severity level. Diabetic retinopathy severity was quantified using the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS). MAIN OUTCOME MEASURES: Two-step or more or 3-step or more improvement or worsening on the ETDRS DRSS and time to new proliferative event (composite end point). RESULTS: At baseline, most patients were distributed evenly among mild or moderate nonproliferative DR (NPDR; ETDRS DRSS, 35/43), moderately severe or severe NPDR (ETDRS DRSS, 47/53), and proliferative DR (ETDRS DRSS, 60-75; 28.8%, 33.2%, and 31.1%, respectively). At month 24, rates of 2-step or more improvement with ranibizumab 0.3 mg, ranibizumab 0.5 mg, and sham treatment were highest among patients with baseline DR levels 47/53 (78.4%, 81.1%, and 11.6%, respectively) compared with patients with baseline DR levels 35/43 (10.3%, 15.8%, and 1.4%, respectively) or 60 through 75 without panretinal photocoagulation (31.0%, 36.4%, and 6.7%, respectively; all ranibizumab vs. sham comparisons, P < 0.05). In patients with baseline DR levels 47/53, ranibizumab treatment reduced the probability of patients experiencing a new proliferative event at month 36 by 3 times compared with sham treatment (12.4% and 11.9% vs. 35.2% for ranibizumab 0.3 mg, ranibizumab 0.5 mg, and sham, respectively). In patients with baseline DR levels 47/53 who achieved 2-step or more DR improvement, improvements were independent of all assessed baseline characteristics (P > 0.4). CONCLUSIONS: Ranibizumab treatment resulted in DR improvements in all 3 baseline DR severity subsets examined. The greatest benefits in DR improvement occurred in patients with baseline moderately severe to severe NPDR (DR levels 47/53). Diabetic retinopathy improvements were rapid, clinically meaningful, and sustained through month 36.

Topical lidocaine gel with and without subconjunctival lidocaine injection for intravitreal injection: a within-patient study.

BACKGROUND AND OBJECTIVE: To determine whether patients prefer topical anesthesia or subconjunctival anesthesia for intravitreal injection. PATIENTS AND METHODS: Consecutive patients receiving bilateral simultaneous injections of anti-vascular endothelial growth factor agents were asked to participate in this within-patient, prospective, single-blinded, randomized, factorial study. Fifty-seven patients completed the study. Both eyes were treated with topical anesthesia. One eye was also injected with subconjunctival lidocaine. Anesthesia for the next treatment visit was based on patient preference at the conclusion of the study visit and at a 4-hour and 24-hour follow-up telephone call. Patients were allowed to change their anesthesia preference during the next three visits. The final endpoint for the study was anesthesia preference for ongoing intravitreal injections. RESULTS: Fifty patients (88%) preferred subconjunctival anesthesia and seven patients (12%) preferred topical anesthesia for ongoing treatments. (P = .0003) CONCLUSION: Given the choice, most patients prefer subconjunctival anesthesia to topical anesthesia for intravitreal injections.