Anatomical Improvement Research Articles

Successful Adjunctive Treatment of Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP) with High-Dose Intravenous Immunoglobulin Therapy (IVIG).

Purpose: The management of bilateral diffuse uveal melanocytic proliferation is controversial, with most earlier reports advocating for plasmapheresis. Here, we report a case of bilateral diffuse uveal melanocytic proliferation secondary to gastric adenocarcinoma that was successfully treated with adjunctive intravenous immunoglobulin, using a loading dose followed by a treat-and-extend strategy. Methods: Clinical case report with 3 years of follow-up including serial ophthalmologic examinations. Functional assessments included visual acuity and subjective visual complaints. Periodic anatomic assessments were performed including serial optical coherence tomography, ultra-widefield fundus imaging, multimodal angiography, and ophthalmic ultrasound. Results: A 75-year-old man presented with a 6-month history of blurry vision and difficulty with dark and light adaptation in both eyes. A diagnosis of bilateral diffuse uveal melanocytic proliferation was established based on clinical findings and subsequent discovery of an underlying gastric malignancy; the diagnosis of a paraneoplastic syndrome was further substantiated by documentation of cancer-associated antiretinal antibodies and serum reactivity against human retina by immunohistochemistry. Treatment with high-dose (2 g/kg) intravenous immunoglobulin was initiated with biweekly, followed by monthly, then q2-3 monthly dosing intervals. Meanwhile, the patient received surgical resection and systemic chemotherapy resulting in complete radiographic remission of the primary cancer. Over the course of 3 years, the patient has demonstrated clinically significant improvements in visual acuity and subjective visual function. Rapid and sustained anatomic improvements were observed in serous retinopathy and choroidal thickness. Conclusion: Intravenous immunoglobulin may be a viable adjunctive treatment option for some patients with bilateral diffuse uveal melanocytic proliferation.

Short-term results of steroid treatment in patients with non-arteritic ischemic optic neuropathy

Aims: To evaluate the effects of steroid treatment on the best-corrected visual acuity (BCVA) and retinal nerve fiber layer (RNFL) in patients with non-arteritic ischemic optic neuropathy (NAION). Methods: The retrospective study included 24 eyes of 24 patients who received 1 gram/day pulse steroid treatment for 3 days with a diagnosis of NAION. The patient's comorbidities, demographic information, intraocular pressure, BCVA, and RNFL measured by optical coherence tomography (OCT) were recorded before and after treatment at one month. Results: The mean age of the patients was 64.35±14.6 (22-86). Diabetes mellitus was present in 14 patients (58.3%), hypertension in 13 (54.2%), and coronary artery disease in 5 (27.8%). The pre-treatment BCVA was 0.33±0.37, and post-treatment BCVA was 0.37±0.36 (p=0.345). The pre-treatment RNFL value was 208.0±57.9, and the post-treatment RNFL value was 113.6±32.6 (p<0.000). No additional complications related to treatment were observed. Conclusion: While there was no significant difference in BCVA values one month after steroid treatment, a significant anatomical improvement was observed in RNFL thickness.

Influence of vortex vein engorgement for photodynamic therapy in central serous chorioretinopathy

This study evaluates the efficacy of photodynamic therapy (PDT) in treating central serous chorioretinopathy (CSC) based on the number of engorged vortex vein draining macula visualized on ultra-widefield (UWF) indocyanine green angiography (ICGA). Thirty-six eyes of 36 patients with treatment-naïve CSC were included. Macula-draining vortex veins were assessed in each quadrant using UWF ICGA. The resolution of subretinal fluid (SRF), pigment epithelial detachment (PED), ellipsoid zone (EZ) disintegrity, and retinal pigment epithelium (RPE) irregularity were evaluated at 3 months after PDT. Visual and anatomical improvements were monitored for 12 months. Logistic regression analysis was performed to identify factors associated with poor visual outcomes. A higher number of macula-draining vortex vein was associated to persistent SRF (p = 0.004), PED (p = 0.001), EZ disintegrity (p = 0.011), and RPE irregularity (p = 0.001). Macula-draining vortex veins were also correlated with poor EZ restoration and limited best corrected visual acuity (BCVA) improvements. In multivariate analysis, the number of macula-draining vortex vein (B = 0.197, p = 0.047) was a risk factor for worse BCVA at 12 months. Increased macula-draining vortex vein was related with unfavorable anatomical and poor visual outcomes after PDT in CSC patients.

Two-year outcomes of intravitreal conbercept therapy for polypoidal choroidal vasculopathy.

This study aims to evaluate the two-year outcomes of polypoidal choroidal vasculopathy (PCV) treated with conbercept and to investigate the predictive response factors. Consecutive patients with PCV who received three-loading intravitreal conbercept, followed by as-needed reinjections, were studied retrospectively. The best corrected visual acuity (BCVA), central retinal thickness (CRT) and polyps were evaluated. Patients who achieved dry maculae in month 6 were categorised into the dry group, or otherwise, into the non-dry group. The predictive factors for a dry macula were evaluated. A total of 25 eyes from 25 patients (17 males; mean age: 62.8 ± 6.4 years) were included. At month 24, the average BCVA increased significantly from 49.9 ± 15.0 letters to 57.2 ± 16.0 letters (p = 0.040); the average CRT decreased significantly from 430.16 ± 166.55μm to 278.31 ± 157.34μm (p = 0.00), and 88% of the eyes achieved dry maculae. The number of polyps changed from 55 to 20 (fading rate: 63.6%; p < 0.001). The mean number of intravitreal injections was 8.6 ± 5.4. The dry group (10 eyes, 40%) was more likely to have higher branching vascular network vessel density (BVN VD; p = 0.021), submacular haemorrhages (p = 0.011) but lack polyp-related serous pigmented epithelial detachment (PED) (p = 0.037). Conbercept was effective in eyes with PCV at maintaining functional and anatomical improvement. Baseline characteristics, including BVN VD, the presence of polyps with serous PED and submacular haemorrhage, seemed to be related to the response to conbercept.

Corneal stromal lenticule transplantation for the treatment of congenital optic disc pit maculopathy : a case report and review

BackgroundCongenital optic disc pit (ODP) is a relatively uncommon congenital anomaly of the optic disc, which seriously affects the patient’s vision when combined with optic disc pit maculopathy(ODP-M). Currently, the treatment of ODP-M remains a clinical challenge and a focus of research.Case presentationA boy had a pit in the inferotemporal segment of the optic disc with ODP-M. Optical Coherence Tomography(OCT) showed ODP and serous retinal detachment. He was treated with pars plana vitrectomy(PPV), followed by Corneal Stromal Lenticule (CSL) sealing and C3F8 tamponade. In the end, significant anatomical improvement was achieved, and the Best Corrected Visual Acuity(BCVA) was improved.ConclusionsThe CSL transplantation may be a viable therapeutic option for improving ODP-M with stable anatomical and functional result. However, more cases and longer follow-up are needed to confirm the safety and effectiveness of the technology.

Therapies for Central Serous Chorioretinopathy: A Report by the American Academy of Ophthalmology

To assess the safety and efficacy of the multiple therapeutic modalities for the treatment of central serous chorioretinopathy (CSCR). A literature search of English-language studies in the PubMed database with no date restrictions was last conducted in May 2024. The combined searches yielded 612 citations, 31 of which were selected for full-text review and for inclusion in this assessment. The panel methodologist assigned a level of evidence rating to each study. Six were assigned a level I rating, 23 were assigned a level II rating, and 2 were assigned a level III rating. Studies were categorized based on treatment modalities: laser-based therapy, intravitreal therapy, laser-based therapy versus intravitreal therapy, and systemic therapies. Within those categories, they were separated based on treatments for acute versus chronic CSCR. One level I study showed that photodynamic therapy (PDT) using half-dose verteporfin for acute CSCR led to a significant decrease in subretinal fluid (SRF) with 95% of treated patients having no SRF at 12 months compared with 58% of untreated eyes with acute CSCR (P= 0.001). Anatomically, the mean CFT at 1 year was significantly lower in the treated group (161 ± 65 μm) versus the observation group (278 ± 92 μm) (P= 0.001). A second level I study compared half-dose verteporfin PDT versus 30%-dose verteporfin PDT and found that 94.6% in the half-dose PDT group had no SRF at 12 months compared with 75.4% in the 30%-dose PDT group (P= 0.004). The noninferiority of the 30%-dose PDT compared with half-dose PDT was not demonstrated. The VICI trial was a level I study that found no benefit with the use of mineralocorticoid antagonism with eplerenone for the treatment of chronic CSCR. With respect to the primary outcome of visual acuity (VA), the VICI trial found no significant difference at 12 months: 79.5 letters in the placebo group and 80.4 letters in the eplerenone group (P= 0.24). In general, the results from the other evaluated studies were inconsistent and thus inconclusive. There were no level I studies that supported the role of intravitreal anti-VEGF injections or systemic beta-blockers for patients with CSCR. A small level I study showed potential efficacy of Helicobacter pylori therapy for CSCR. There is evidence to support half-dose PDT for the treatment of acute CSCR regarding anatomic improvement, but less robust evidence supports improvement in VA or sustained anatomic benefit beyond 12 months. Intravitreal anti-VEGF injections and oral beta-blockers demonstrate inconsistent anatomic and visual benefits in patients with CSCR. The mineralocorticoid antagonist eplerenone has not been demonstrated as efficacious for treatment of chronic CSCR. The treatment of H.pylori infection may have some anatomic and visual benefit in the treatment of either acute or chronic CSCR. Acute CSCR resolves spontaneously without treatment in most eyes. Proprietary or commercial disclosure may be found after the references.

Intravitreal faricimab for treatment naïve patients with neovascular age-related macular degeneration: a real-world prospective study

BackgroundIntravitreal faricimab, a bispecific antibody targeting both angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A), was recently introduced for the treatment of neovascular age-related macular degeneration (nAMD), diabetic macular oedema and cystoid macular oedema secondary to retinal vein occlusion. The aim of our study was to assess the efficacy, safety and durability of intravitreal faricimab in a real-world cohort of treatment-naïve patients with nAMD.MethodsSingle-centre, prospective cohort study of 21 eyes from 19 treatment-naïve nAMD patients who were treated with intravitreal faricimab from October 2022 to April 2024. Patients underwent a loading dose (LD) of 4 monthly faricimab injections followed by a treat-and-extend regimen. Primary outcomes included best-corrected visual acuity (BCVA) and structural parameters from spectral-domain optical coherence tomography (SD-OCT). Secondary outcomes included the proportion of eyes achieving a dry macula, maximal fluid-free interval and intended interval at last follow-up.ResultsThe study included 21 eyes of 19 patients (mean age 83.1 years). After LD, 93.3% of eyes achieved a dry macular SD-OCT scan within a median time of 8 weeks. At the first extension, 53% of eyes remained dry, while 47% showed fluid recurrence. Long-term analysis (n = 14) revealed significant reductions in macular volume (MV), central subfield thickness (CST), and pigment epithelial detachment (PED) height over a median follow-up of 64.9 weeks, with sustained visual and anatomical improvements. Median BCVA, CST, and MV at the final follow-up were significantly improved from baseline (p < 0.01). The intended interval between injections was ≥ 12 weeks in 42.86% of eyes. No cases of intraocular inflammation were observed, although 10% experienced retinal pigment epithelial tears.ConclusionsIntravitreal faricimab demonstrated favourable efficacy, safety, and durability outcomes in a real-world cohort of treatment-naïve nAMD patients.

Fluocinolone acetonide 0.18-mg implant for treatment of recurrent inflammation due to non-infectious uveitis: a case series of 15 patients

IntroductionUncontrolled non-infectious uveitis affecting the posterior segment (NIU-PS) can lead to vision loss due to repeated bouts of inflammation and consequent tissue damage. Patients with chronic NIU-PS who experience recurrent uveitis after being treated with systemic and short-acting local corticosteroids may benefit from the sustained-release 0.18-mg fluocinolone acetonide implant (FAi).MethodsIn this case series, 18 eyes with chronic, recurrent NIU-PS and cystoid macular edema (CME) treated with the 0.18-mg FAi were analyzed retrospectively. Data on patient demographics, clinical history, previous and concomitant treatments for uveitis recurrence, time to and number of uveitis recurrences, intraocular pressure (IOP), central subfield thickness (CST), and visual acuity (VA) were collected and summarized.ResultsA majority of patients (14/15 [93%]) had a history of ocular surgery, largely cataract extraction, and all developed chronic and recurrent NIU-PS and CME. At baseline, patients had a mean age of 72 years (range: 46 to 93), were 53% male, and had a mean duration of NIU-PS of 3 years (range: 1 to 19). Patients were followed for an average of 16.5 months (range: 2 to 42.5 months) post FAi. Eleven of the 18 eyes (61%) had ≥ 5 recurrences of uveitis since diagnosis, with an average time to recurrence of approximately 12 weeks (range: 1 to 27). All eyes treated with the 0.18-mg FAi showed reduced NIU-PS recurrence and visual and anatomical improvement, as measured by VA and CST, respectively. Two eyes had an IOP elevation that was managed with topical therapy, and one eye was treated with topical prednisolone for additional inflammation management. Two eyes required adjunct therapy with short-acting intravitreal corticosteroids at 7 and 16 weeks for NIU-PS recurrence after 0.18-mg FAi insertion.ConclusionAfter receiving the 0.18-mg FAi, eyes with uncontrolled NIU-PS had sustained resolution of CME and inflammation with limited need for supplementary steroid drops or injections and minimal steroid class-specific adverse effects; none required incisional IOP-lowering surgery.

Gene Therapy for Achromatopsia.

Achromatopsia is the most common cone dysfunction syndrome, affecting 1 in 30,000 people. It is an autosomal recessive disorder with a heterogeneous genetic background with variants reported in CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, and ATF6. Up to 90% of achromatopsia patients harbour mutations in CNGA3 or CNB3, which encode for the alpha and beta subunits of the cone cyclic nucleotide-gated (CNG) channel in cone-specific phototransduction. The condition presents at birth or early infancy with poor visual acuity, nystagmus, photophobia, and colour vision loss in all axes. Multimodal retinal imaging has provided insightful information to characterise achromatopsia patients based on their genotype. There is no FDA-approved treatment for achromatopsia; however, studies have reported several preclinical gene therapies with anatomical and functional improvements reported in vivo. There are currently five gene therapy clinical trials registered for human patients at the phase I/II stage and for CNGA3 or CNGB3 causing achromatopsia. This review aims to discuss the genetics of achromatopsia, genotypic and phenotypic correlations in multimodal retinal imaging, and the developments and challenges in gene therapy clinical trials.

Dual pathway inhibition with faricimab for previously treated neovascular age-related macular degeneration and diabetic macular oedema: guidance from a UK panel of retina specialists.

Some eyes with neovascular age-related macular degeneration (nAMD) and centre-involving diabetic macular oedema (DMO) fail to respond sufficiently or lose response over time to standard of care intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. This paper explores clinical scenarios for switching to dual action angiopoietin-2 (Ang-2)/VEGF-A inhibitor faricimab (Vabysmo, Roche Products Limited) in previously anti-VEGF-treated patients. A national steering group meeting of UK retina specialists was held in London on 27 October 2023. Clinician practice and experience were reviewed together with pivotal clinical trial data and early findings from real-world settings. Roche Products Limited facilitated and funded the meeting. While there is no standardised protocol for identifying suboptimal response, the authors review relevant clinical biomarkers of disease activity used in routine clinical practice to determine patient response and guide treatment decisions. Common reasons identified for considering a change of treatment were lack of efficacy demonstrated by suboptimal anatomic or visual improvement and insufficient durability of response. The panel outline strategies for switching to faricimab among eligible patients with a prior anti-VEGF treatment history, with initial monthly loading doses or maintaining the previous treatment interval before attempting to extend, that may be integrated into current treat-and-extend (T&E) clinical pathways for treating patients with nAMD and DMO. General considerations for switching between treatments are also reviewed. Clinicians may consider a treatment switch to faricimab in nAMD and DMO patients who have suboptimal disease control or insufficient durability of response on initial anti-VEGF therapy.

Short-term Outcomes of Faricimab for Neovascular Age-related Macular Degeneration with Limited Response to Ranibizumab or Aflibercept

Purpose: To evaluate the clinical outcomes of switching to faricimab for patients with neovascular age-related macular degeneration (AMD) demonstrating a limited response to prior anti-vascular endothelial growth factor (VEGF) treatments.Methods: We performed a retrospective analysis of patients with neovascular AMD who had residual subretinal fluid (SRF) or intraretinal fluid (IRF) despite treatment with ranibizumab or aflibercept, and who were subsequently treated with faricimab. The study assessed changes in best-corrected visual acuity (logarithm of the minimum angle of resolution) and central retinal thickness (CRT), as well as differences in the incidence of SRF, IRF, and serous retinal pigment epithelial detachment (S-PED) with versus without switching to faricimab.Results: The study included 22 eyes. Mean best-corrected visual acuity improved from 0.31 ± 0.21 before switching to faricimab to 0.28 ± 0.19 after the switch (&lt;i&gt;p&lt;/i&gt; = 0.172). CRT significantly decreased from 336.7 ± 83.3 to 279.9 ± 51.1 μm (&lt;i&gt;p&lt;/i&gt; = 0.002). Prior to switching, SRF was noted in 17 patients (94.4%), IRF in 5 (27.8%), and S-PED in 4 (22.2%). Following the switch to faricimab, these figures dropped to 13 (72.2%), 4 (22.2%), and 3 (16.7%), respectively. A complete resolution of retinal edema was achieved in four patients (22.2%) after the treatment switch.Conclusions: Switching to faricimab in patients with neovascular AMD who had a limited response to previous treatments led to significant anatomical improvements. Faricimab may be a valuable treatment option for these patients.

Revolutionizing Adult Micrognathia Treatment: Should Free Fibular Flap Become an Option?

The management of micrognathia in adults necessitates intricate surgical procedures. A vascularized bone graft, notably the free fibular flap (FFF), offers a novel viable solution for repairing significant defects. However, the limited utilization of FFF in adult micrognathia contributes to gaps in understanding its outcomes. A retrospective case series of 2 patients aged 28 and 65, with severe micrognathia due to neglected trauma and osteoradionecrosis, underwent refracture and reconstruction with FFF. Intraoperatively, no significant complications occurred. The FFF were molded to fit the gaps of refractured mandible sites, with similar surgical approaches for both patients. Upon 3 months' follow up, their quality of life (QoL), structural changes, and sensation alterations were assessed and showed promising results. The sensory impairment caused did not hinder the quality of life. Thus, the free fibular flap demonstrates promising outcomes as the initial treatment for adult micrognathia, yielding minimal morbidities and significant functional and anatomic improvements.

Efficacy, durability, and safety of faricimab with extended dosing up to every 16 weeks in diabetic macular edema: 2-year results from the Japan subgroup of the phase 3 YOSEMITE trial

PurposeTo evaluate the 2-year efficacy, durability, and safety of faricimab in patients with diabetic macular edema (DME) in the YOSEMITE Japan subgroup.Study designYOSEMITE/RHINE (NCT03622580/NCT03622593) subgroup analysis: global, multicenter, randomized, double-masked, active-comparator–controlled, phase 3 faricimab trials.MethodsPatients were randomized 1:1:1 to intravitreal faricimab 6.0 mg every 8 weeks (Q8W) and per treat-and-extend (T&E) dosing, or aflibercept 2.0 mg Q8W. Outcomes were assessed through year 2 for the YOSEMITE Japan subgroup (N = 60) and the pooled YOSEMITE/RHINE global cohort (N = 1891).ResultsIn the YOSEMITE Japan subgroup, 21, 19, and 20 patients were randomized to faricimab Q8W, faricimab T&E, and aflibercept Q8W, respectively (632, 632, and 627 patients in the pooled YOSEMITE/RHINE cohort). Vision gains and anatomic improvements with faricimab at year 1 were maintained over 2 years and were generally consistent between groups. Mean best-corrected visual acuity changes from baseline at year 2 (weeks 92–100 average) for the YOSEMITE Japan subgroup were +12.5, +9.0, and +5.0 letters in the faricimab Q8W, faricimab T&E and aflibercept Q8W arms, respectively (+10.8, +10.4, and +10.3 letters in the pooled YOSEMITE/RHINE cohort). At week 96, 61.1% of the YOSEMITE Japan subgroup and 78.1% of the pooled YOSEMITE/RHINE cohort were on ≥ Q12W dosing. Faricimab was well-tolerated with a safety profile comparable with aflibercept.ConclusionFaricimab up to Q16W offered durable vision gains and anatomic improvements up to 2 years in patients with DME in the YOSEMITE Japan subgroup. Outcomes were generally consistent with the pooled YOSEMITE/RHINE cohort.

Functional and anatomical results of subthreshold micropulse laser as rescue treatment for central serous chorioretinopathy after verteporfin shortage

BackgroundTo evaluate the anatomical and functional outcomes of high-density subthreshold micropulse laser (HSML) treatment in a cohort of patients diagnosed with chronic central serous chorioretinopathy (CSCR) whose treatment with photodynamic therapy (PDT) was delayed due to the worldwide shortage of verteporfin. MethodsProspective interventional study which included 42 eyes of 40 patients diagnosed with chronic CSCR and on the waiting list for PDT who received rescue therapy with HSML using the Navilas® System device (OD-OS GmBH, Teltwo, Germany). Best corrected visual acuity (BCVA), subretinal fluid (SRF), and subfoveal choroidal thickness (SFCT) were measured at inclusion and during the follow-up visits at 2, 4, and 6 months. ResultsThe mean waiting time from the indication of PDT until treatment with HSML was 14.6 ± 9.7 months (range 5–21). There were no differences in the pre-treatment BCVA compared with the 6-month follow-up visit (67 ± 16.7 letters and 67.5 ± 8.2 letters respectively, p = 0.136). However, there was a significant decrease in the mean SFCT of -39.6 ± 37.1 μm (p = 0.030). Additionally, there was a decrease in SRF height between the pre-treatment measure (123.0 ± 49.8 μm) and the 2, 4, and 6-month follow-up visits after HSML of -58.5 ± 68.2 μm, -53.2 ± 76.3 μm, and -65.4 ± 53.6 μm respectively (p < 0.001). A complete resolution of the SRF was observed in 16/42 eyes (38.1 %) and a reduction of the SRF height in 85.7 % of the overall cohort was observed after HSML treatment. ConclusionA significant anatomical improvement in SRF and a decrease in SFCT were observed in patients with CSCR who were previously waiting for PDT and were rescued by HSML. However, the rate of complete SRF resolution was low.

One-year Clinical Outcome of Topical Bromfenac in Central Serous Chorioretinopathy

Purpose: To evaluate the efficacy of topical bromfenac in treating central serous chorioretinopathy (CSC) over a 1-year period.Methods: A retrospective analysis was conducted on 57 patients (57 eyes) with CSC followed for &gt; 1 year. Patients were divided into two groups: those treated with bromfenac eye drops twice daily (29 eyes) and a control group (28 eyes). Best-corrected visual acuity (BCVA), central macular thickness (CMT), and subretinal fluid (SRF) height were measured and compared between the two groups as was the proportion of chronic cases.Results: Significant improvements in CMT and SRF height were noted in both groups over the follow-up period. The bromfenac group demonstrated significantly lower CMT at 6, 9, and 12 months (p = 0.045, 0.042, and 0.023, respectively) and lower SRF height (p = 0.037, 0.048, and 0.046, respectively) compared to the control group. The proportion of chronic cases was significantly lower in the bromfenac group (17.2%) compared to the control group (42.9%, p = 0.035).Conclusions: Topical bromfenac reduced the rate of progression to chronic CSC and showed significant anatomical improvements after 6 months, suggesting its potential as an effective treatment option.

Anti-VEGF therapy for the long-term management of diabetic macular edema: a treat-to-target strategy based on macular morphology.

In an aging population, the prevalence and burden of diabetes mellitus, diabetic retinopathy, and vision-threatening diabetic macular edema (DME) are only expected to rise around the world. Similarly to other complications of diabetes mellitus, DME requires long-term management. This article aims to review the current challenges associated with the long-term management of DME, opportunities to improve outcomes for patients, and to develop a treat-to-target strategy based on macular morphology. At present, intravitreal anti-vascular endothelial growth factor (VEGF) therapy is the standard of care for the management of DME; however, best-achievable vision outcomes with treatment are reliant on frequent injections and close monitoring, which are difficult to maintain in current clinical practice because of the burden this imposes on patients. Achieving and maintaining good vision with treatment are the most important factors for patients with DME. Landmark trials have shown that vision gains with anti-VEGF therapy are typically accompanied by anatomical improvements (e.g., reductions in retinal thickness); therefore, multimodal imaging measures of macular morphology are often used in patients with DME to guide real-world treatment decisions. We would like to propose a hypothetical treat-to-target algorithm to guide physicians on treatment strategies for the long-term management of DME. Alternative measures of retinal fluid (e.g., persistence, stability, location) may be stronger predictors of visual acuity in DME, although further research is required to confirm whether alternate quantifiable biomarkers such as subretinal fluid and intraretinal fluid volumes can be used as a biomarker of clinical improvement. Identifying novel biomarkers and treatments that target neuroinflammation and neurodegeneration, improving patient-physician communication around treatment adherence, and using treat-to-target measures may help to ensure that the long-term benefits of treatment are realized.

Real world efficacy and durability of faricimab in patients with neovascular AMD (nAMD) who had sub-optimal response to prior anti-VEGF therapy.

Age-related macular degeneration (AMD) remains a primary cause of blindness, with neovascular AMD (nAMD) presenting particular treatment challenges. Despite anti-vascular endothelial growth factor (anti-VEGF) therapies, many patients exhibit a suboptimal response to the previously available anti-vascular endothelial growth factor (anti-VEGF) therapies. This study evaluates the efficacy and treatment interval extension of faricimab in this patient cohort. In a retrospective single-centre study at University Hospitals of Bristol and Weston, UK, nAMD patients suboptimally responsive to previous anti-VEGF therapies were switched to faricimab. Treatment started with an initiation phase of 4 monthly injections followed by a 'Treat and Extend' protocol. Outcomes included best-recorded visual acuity (BRVA), central subfield thickness (CST), the presence of retinal fluid, and treatment intervals. Among 98 eyes of 79 patients, following faricimab treatment, significant reductions in CST and retinal fluid were noted, indicating decreased disease activity. While BRVA changes were not statistically significant, the anatomical improvements suggest a potential therapeutic benefit. Notably, 40% of patients achieved extended treatment intervals, reducing the treatment burden. Faricimab offers a promising alternative for nAMD patients with suboptimal responses to prior anti-VEGF treatments, demonstrating significant anatomical improvements and the possibility of extended dosing intervals. These findings highlight the need for prospective real-world studies to further assess faricimab's role in nAMD management and its long-term impact on patient outcomes.

Effectiveness of Suprachoroidal Injection of Triamcinolone Acetonide in Diabetic Macular Edema Following Pars Plana Vitrectomy Using a Modified Custom Microneedle.

The present study evaluated the efficacy of suprachoroidal injection of Triamcinolone Acetonide (SCTA) in diabetic macular edema (DME) following pars plana vitrectomy (PPV) using a modified microneedle. A prospective interventional study was conducted on 60 eyes of 60 patients with centrally involved diabetic macular edema following pars plana vitrectomy (PPV). SCTA was performed at the baseline and repeated after 3 months in case of persistent subretinal or intraretinal fluid, central macular thickness (CMT) more than 300 µm or visual loss by more than one line of the Snellen chart. The present study detected significant reduction of the CMT from 498.3 ± 94.8 µm at the baseline to 212.3 ± 11.9 µm after 12 months of injection with p < 0.001 and a significant improvement of best corrected visual acuity (BCVA) from 1 (0.9-1.2) at the baseline to 0.5 (0.3-0.7) after 12 months of injection with p < 0.001. The intraocular pressure (IOP) increased significantly after 3 months of injection with p < 0.001 and then gradually declined to its normal level after 6 months. Inner segment/outer segment (IS/OS) disruption was the only significant predictor of the final CMT; however, the number of injections, IS/OS disruption, baseline BCVA and the HbA1C level were the significant predictors of the final BCVA after injection. Suprachoroidal injection of TA using this microneedle resulted in significant anatomical and functional improvement in previously vitrectomized diabetic macular edema patients with no recorded ocular or systemic adverse events.

Clinical Characteristics of Proliferative Diabetic Retinopathy and Outcome of Pars Plana Vitrectomy in Proliferative Diabetic Retinopathy.

Proliferative diabetic retinopathy is a leading cause of blindness among people with diabetes. The study aimed to assess the clinical characteristics of proliferative diabetic retinopathy and outcome of pars plana vitrectomy in Proliferative diabetic retinopathy. A prospective study was conducted from September 2019 to December 2021 among consecutive cases of proliferative diabetic retinopathy who underwent pars plana vitrectomy at a tertiary eye care center. Study was conducted after ethical approval from Institutional Review Committee. Detailed systemic and ocular history, visual acuity, ocular findings under mydriasis, surgical procedures, and outcome following pars plana vitrectomy were recorded. Cases were followed up regularly until one year after the pars plana vitrectomy. Total of 83 cases (89 eyes) of proliferative diabetic retinopathy were enrolled in the study. The mean age was 53 years ±9.7 SD, ranging from 26 years to 72 years. Males comprised of 62.7% cases. Type two diabetes comprised of 94% of cases. Indications for pars plana vitrectomy were; mixed vitreous hemorrhage and tractional retinal detachment (38.2%), non-clearing vitreous hemorrhage (38.1%), and tractional retinal detachment only (24.7%). Pre-operative intra-vitreal anti-vascular endothelial growth factor was given in 78.65% eyes and pan retinal photocoagulation in 58.42% eyes. The anatomical success was achieved in 95.5% eyes, visual improvement in 68.54%, static in 14.6% and worsened in 16.86% of eyes. About 15.7% of eyes had some form of post- operative complications. Vitreous hemorrhage with tractional retinal detachment, persistent vitreous hemorrhage and tractional retinal detachment involving macula were the common indication of pars plana vitrectomy among cases of Proliferative diabetic retinopathy. Anatomical success and visual acuity improvement can be achieved in majority of the eyes following PPV in Proliferative diabetic retinopathy.

Faricimab for neovascular age-related macular degeneration and diabetic macular edema: from preclinical studies to phase 3 outcomes

AbstractIntravitreal anti–vascular endothelial growth factor (VEGF) therapy is the standard of care for diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD); however, vision gains and anatomical improvements are not sustained over longer periods of treatment, suggesting other relevant targets may be needed to optimize treatments. Additionally, frequent intravitreal injections can prove a burden for patients and caregivers. Angiopoietin-2 (Ang-2) has been explored as an additional therapeutic target, due to the involvement of Ang-2 in DME and nAMD pathogenesis. Recent evidence supports the hypothesis that targeting both VEGF and Ang-2 may improve clinical outcomes in DME and nAMD compared with targeting VEGF alone by enhancing vascular stability, resulting in reduced macular leakage, prevention of neovascularization, and diminished inflammation. Faricimab, a novel bispecific antibody that targets VEGF-A and Ang-2, has been evaluated in clinical trials for DME (YOSEMITE/RHINE) and nAMD (TENAYA/LUCERNE). These trials evaluated faricimab against the anti-VEGFA/B and anti–placental growth factor fusion protein aflibercept, both administered by intravitreal injection. In addition to faricimab efficacy, safety, and pharmacokinetics, durability was evaluated during the trials using a treat-and-extend regimen. At 1 year, faricimab demonstrated non-inferior vision gains versus aflibercept across YOSEMITE/RHINE and TENAYA/LUCERNE. In YOSEMITE/RHINE, faricimab improved anatomic parameters versus aflibercept. Reduction of central subfield thickness (CST), and absence of both DME and intraretinal fluid were greater in faricimab- versus aflibercept-treated eyes. In TENAYA/LUCERNE, CST reductions were greater for faricimab than aflibercept at the end of the head-to-head phase (0–12 weeks), and were comparable with aflibercept at year 1, but with less frequent dosing. CST and vision gains were maintained during year 2 of both YOSEMITE/RHINE and TENAYA/LUCERNE. These findings suggest that dual Ang-2/VEGF-A pathway inhibition may result in greater disease control versus anti-VEGF alone, potentially addressing the unmet needs and reducing treatment burden, and improving real-world outcomes and compliance in retinal vascular diseases. Long-term extension studies (RHONE-X, AVONELLE-X) are ongoing. Current evidence suggests that dual inhibition with faricimab heralds the beginning of multitargeted treatment strategies inhibiting multiple, independent components of retinal pathology, with faricimab providing opportunities to reduce treatment burden and improve outcomes compared with anti-VEGF monotherapy.