Intravitreal Injection Research Articles

Intravitreal therapy in neovascular age-related macular degeneration-adapting to increasing demand and changing times.

To report the outcomes of patients with neovascular age-related macular degeneration (nAMD) at Palmerston North Eye Clinic (PNEC) during 2020 and 2021, comparing time to treatment initiation based on nurse-injector availability and during COVID-19 restrictions. Data were recorded from a prospective database for patients with nAMD at PNEC. Each patient's electronic health record was reviewed to ensure the accuracy of the database and to fill in missing data points. Statistics were done using Microsoft Excel and R. One hundred and fifty-six eyes were diagnosed with nAMD during the study. Mean time from referral triage to first injection was 13.08 days across the study period. Time to treatment initiation was not statistically different by level of COVID-19 restriction but there was a significant difference in first specialist appointment to injection interval when three nurse-injectors were available compared to four. The effect seemed most evident in subsequent months after reduced nurse-injector availability began. Despite an increase in nAMD diagnoses each year, PNEC continues to meet national guidelines for interval from referral to treatment initiation through innovations in practice. As demand for intravitreal injections continues to increase, further resourcing and research into newer agents will be required to keep wait times compliant with guidelines.

Impact of glucagon-like peptide-1 receptor agonists on diabetic retinopathy: A meta-analysis of clinical studies emphasising retinal changes as a primary outcome.

To determine if glucagon-like peptide-1 receptor agonists (GLP-1RA) are associated with the development and progression of diabetic retinopathy (DR). A systematic search was conducted on PubMed, Cochrane Library, and Embase from inception to February 2024 to identify clinical studies reporting the development of and changes in DR as the primary outcome in patients with type 2 diabetes taking GLP-1RA, insulin, or oral antidiabetic medication (OAD). Two researchers independently completed the search and referred to a third as necessary. Data for meta-analysis was pooled using a random-effects model. Analysis of seven studies representing 242 537 patients showed a significantly decreased risk of incidence of DR between GLP-1RA and insulin use (RR = 0.66, 95% CI (0.48, 0.91), p = 0.01). There was no difference in the risk of DR complications (e.g., vitreous haemorrhage, retinal detachment, or requiring treatment with intravitreal injections, lasers, vitrectomy). Between GLP-1RA and OAD use, there was no difference in the risk of incidence of DR, while there was a significantly increased risk of DR complications (RR = 1.39, 95% CI (1.07, 1.80), p = 0.01). Our findings indicate no elevated risk of incidence of DR linked to GLP-1RA compared to insulin. In fact, GLP-1RA may offer potential advantages over insulin regarding the overall incidence of DR. The increased risk of DR requiring treatment and associated complications in the GLP-1RA group compared to OAD may be due to the transient progression of DR associated with a rapid decrease in HbA1c - a phenomenon not specific to GLP-1RA and warrants further investigation.

Settings and Clinical Applications of Subthreshold Micropulse Laser Therapy: A Review.

Subthreshold lasers operate below the threshold of visible tissue damage, thereby preventing ophthalmoscopically visible thermal damage to the chorio-retinal layers. They could represent a safe and effective alternative and/or adjunctive procedure to conventional lasers in treating diabetic macula edema (DME), central serous chorioretinopathy (CSCR), and branch retina vein occlusion (BRVO). This review focuses on the use of subthreshold micropulse laser (SMPL), its settings, and clinical applications. Despite their widespread use, a standardized protocol for sub-threshold laser settings has not been established yet, and thus, there is uncertainty in selecting effective and safe parameters for any specific situation. We conducted a comprehensive overview of the existing indications for subthreshold laser therapy and their settings for different retinal diseases. The debate revolves around which parameters could guarantee the safety of the procedure for each case, depending on the duty cycle, the laser wavelength, the spot duration, and the power, with laser power titration on one side or choosing a fixed lowered power value on the other side. SMPL therapy for DME, CSCR, and BRVO-associated macular edema has shown significant effectiveness in reducing the macular thickness, facilitating subretinal fluid absorptions, increasing the best corrected visual acuity (BCVA) and reducing the number of intravitreal injections (IVI) required annually. We presented a broad list of the laser parameters reported in the literature, organized into different tables divided based on the specific pathology, with the aim of providing a useful tool for future studies.

Dynamics of Treatment Response to Faricimab for Diabetic Macular Edema.

This study analyzes the dynamics of short-term treatment response to the first intravitreal faricimab injection in eyes with diabetic macular edema (DME). This retrospective, single-center, clinical trial was conducted at the Department of Ophthalmology, University Hospital Zurich. Patients with treatment-naïve and pretreated DME were included. Patient chart data and imaging were analyzed. Safety and efficacy (corrected visual acuity (CVA), central subfield thickness (CST), and signs of intraocular inflammation (IOI)) of the first faricimab intravitreal therapy (IVT) were evaluated weekly until 4 weeks after injection. Forty-three eyes (81% pretreated) of 31 patients were included. Four weeks after the first faricimab IVT, CVA remained stable and median CST (µm) decreased significantly (p < 0.001) from 325.0 (293.5-399.0) at baseline to 304.0 (286.5-358.0). CVA at week 4 was only associated with baseline CVA (p < 0.001). CST was the only predictive variable (p = 0.002) between baseline and week 4 CST. Weekly safety assessments did not show any sign of clinically significant IOI. This study suggests faricimab is an effective treatment for (pretreated) DME, showing structural benefit 1 month following the first injection without short-term safety signals.

A cost-minimization analysis of anti-VEGFs for the treatment of neovascular age-related macular degeneration in the Netherlands.

Age-related macular degeneration (AMD) is the main cause of severe vision loss globally. Neovascular AMD (nAMD) is an advanced stage of AMD treated with anti-vascular endothelial growth factors (anti-VEGFs). Although anti-VEGF treatment is effective, the frequent intravitreal injections place a burden on patients, (in)formal caregivers, and clinics. This study assesses the health-economic impact of anti-VEGF agents with lower injection frequency that have the potential to reduce treatment burden and compares it to the standard of care. We developed a cost-minimization model to evaluate the direct medical costs associated with first-line unilateral anti-VEGF treatment across a 3-year time horizon in the Netherlands. The analysis compared aflibercept 8mg, aflibercept 2mg, bevacizumab, faricimab, and ranibizumab. Our model adopted a treat-and-extend (T&E) regimen for aflibercept 2mg, bevacizumab, and ranibizumab. For aflibercept 8mg, a flexible regimen that was extendable up to 24weeks was applied, while faricimab followed a flexible regimen that was extendable up to 16weeks. Additionally, since list prices may vary from net prices, we calculated the break-even price for each anti-VEGF in comparison to bevacizumab, which is the recommended first-line treatment due to its low medication price. Based on list prices, aflibercept 8mg led to the lowest treatment costs (€16,251 per patient over a 3-year time horizon), closely followed by bevacizumab (€17,616 per patient over a 3-year time horizon). Ranibizumab led to the highest per-patient costs (€31,746 over a 3-year time horizon). For bevacizumab, most costs were attributable to administration, while for the other anti-VEGFs, most were attributable to medication. Aflibercept 8mg is cost-saving compared to bevacizumab at their medication prices at the time of writing. Aflibercept 2mg, faricimab, and ranibizumab should be priced below €488, €591, and €75, respectively. To be cost-equal to bevacizumab with current list prices, anti-VEGFs should be administered with a maximum of 12.7 to 13.8 injections over a 3-year time horizon. According to the injection frequency observed in clinical trials, aflibercept 8mg would be the anti-VEGF that generates the lowest per-patient healthcare costs for the treatment of nAMD in the Netherlands after a treatment period of three years. Our study indicates that anti-VEGF drugs with a lower injection frequency might provide a cost-saving solution to the increasing burden of anti-VEGF treatment on the healthcare system.

Anterior Subtenon Triamcinolone Injection for Refractory Macular Edema: A Retrospective Case Series.

To evaluate the effectiveness of anterior subtenon triamcinolone (AST) injections in the management of refractory macular edema. This is a retrospective case series of consecutive eyes with refractory macular edema treated with AST at a single vitreoretinal surgeon's practice at Toronto Western Hospital, University of Toronto, Canada in 2018-2023. Refractory was defined as persistent macular edema with a central subfield thickness of 250μm or greater over a 24-week period, receiving at least four intravitreal anti-VEGF injections. Vision outcomes and optical coherence tomography features for all eyes were compared for three visits pre-AST treatment and two visits post-AST treatment. Ninety-three patients (119 eyes; diabetic macular edema (26%), and pseudophakic CME (74%), with a mean follow-up duration of 161 days were included. The presence of subretinal fluid (p=0.0013), central subfield macular thickness (p<0.0001), cube average thickness (p=0.0024) and macular cube volume (p= 0.0017) significantly improved from pre-AST to post-AST treatment. Visual acuity also significantly improved from pre-AST treatment to post-AST treatment (p<0.0001). There was no significant change in the intraocular pressures from pre-AST to post-AST (p=0.7920) and no complications were noted throughout the follow-up period. The findings from this study suggest that AST injections show modest improvement in anatomical and functional outcomes, and are safe for the treatment and management of refractory macular edema.

Histamine H3 receptor antagonist/nitric oxide donors as novel promising therapeutic hybrid-tools for glaucoma and retinal neuroprotection

Glaucoma is a degenerative optic neuropathy in which the degeneration of optic nerve and blindness occur. The main cause is a malfunction of ciliary processes (protrusions of the ciliary bodies) resulting in increased intraocular pressure (IOP). Ocular hypertension (OHT) causes ischemic events leading to retinal ganglion cell (RGC) depletion and blindness.Histaminergic and nitrergic systems are involved in the regulation of IOP. Therefore, we developed novel hybrid compounds that target histamine H3 receptor (H3R) with nitric oxide (NO) releasing features (ST-1989 and ST-2130). After H3R binding was proven in vitro, we investigated their effects in two OHT models in New Zealand White rabbits. Compound ST-1989 showed the highest NO elevation, together with antioxidative and anti-inflammatory features partly superior to the co-administered H3R antagonist (ciproxifan) and NO donor (molsidomine). This hybrid compound demonstrated IOP reduction in both OHT models induced by intravitreal injection of hypertonic saline and carbomer into the anterior chamber of the eye, respectively. Ocular perfusion and photoreceptor neuroprotection were evaluated in a model of ischemia/reperfusion (I/R) of the ophthalmic artery induced by repeated sub-tenon injections of endothelin-1 (ET-1), twice a week for six weeks. Compound ST-1989 counteracts retinal degeneration reducing ophthalmic artery resistance index and increasing photoreceptor responses, thus rescuing RGCs.Our results indicate that compound ST-1989 is a promising molecule with long-lasting hypotensive effects and good effectiveness in reducing inflammation, oxidative stress, and RGCs apoptosis. In conclusion, these hybrid compounds could be a novel strategy to combat glaucomatous blindness and RGC depletion for ocular diseases involving retinal damage.

Clinical Observation of Micropulse Laser Combined with Conbercept in the Treatment of Neovascular Age-related Macular Degeneration with Pigment Epithelial Detachment (PED)

The aim of this study is to observe the efficacy of micropulse laser combined with Conbercept in the treatment of neovascular age-related macular degeneration (nAMD) complicated with PED. Thirty patients (30 eyes) diagnosed with nAMD and PED at our hospital in 2023 were randomly divided into two groups: the Conbercept treatment (IVC) group with 15 cases (15 eyes) and the Conbercept combined with 577 nm threshold micropulse laser treatment (IVC+SMLP) group with 15 cases (15 eyes). Anti-VEGF treatment was administered according to the 3+PRN regimen, and the combined treatment group received 577 nm threshold micropulse laser treatment within 2 weeks after anti-VEGF injection. Follow-up observed the best-corrected visual acuity (BCVA), central macular thickness (CMT), PED height (PEDH), number of injections, and related complications at 1 month, 3 months, 6 months, and 12 months after Conbercept intravitreal injection. The average BCVA, CMT, and PEDH in both groups improved significantly from baseline at all time points (P &lt; 0.05). At 12 months of follow-up, PEDH in the IVC+SMLP group decreased significantly from baseline (293.57±82.59 vs 184.84±33.95) and was significantly lower than in the IVC group (P &lt; 0.05). The number of IVC injections in the IVC group was significantly higher than in the IVC+SMLP group (8.04±0.3 vs 5.29±1.26) with a significant difference (t=4.290, P=0.016). No treatment-related adverse events were observed during the study. The 577 nm threshold micropulse laser combined with Conbercept effectively improves or stabilizes visual function and anatomical morphology in nAMD with PED, reduces the number of intravitreal injections, and alleviates the patient's economic burden to some extent.

Managing massive submacular hemorrhage using intravitreal brolucizumab in combination with subretinal tissue plasminogen activator and non-expansile gas – A case report

We report a case of a 60-year-old lady presented to us with a sudden painless diminution of vision in the left eye (LE). Her best-corrected visual acuity (BCVA) was counting fingers close to face in the LE. She was diagnosed with submacular hemorrhage (SMH) secondary to polypoidal choroidal vasculopathy (PCV). We performed a standard 25-gauge pars plana vitrectomy with subretinal tissue plasminogen activator injection along with an intravitreal injection of brolucizumab and perfluoro propane (C3F8) gas injection. Six weeks after the procedure, her BCVA improved to counting fingers at three meters. After another two injections of brolucizumab at one-month intervals, the BCVA improved to 6/9, N6. We present the long-term follow-up of this eye for nearly 18 months with improved visual acuity, that is, 6/36, N24 at the final visit. This technique shows favorable results in the case of massive SMH due to PCV.

Pain perception during intravitreal injections is related to the timing of instilling anesthetic eyedrops

Pain perception during intravitreal injections is related to the timing of instilling anesthetic eyedrops

Intravitreal steroid implants in the management of noninfectious intermediate and posterior uveitis

Abstract The management of intermediate and posterior uveitis poses a significant challenge of achieving adequate drug concentrations in the posterior segment over the chronic nature of the disease. Systemic agents seldom reach effective drug levels, and even with low maintenance or tapering doses, it is hard to avoid systemic toxicity. The use of intravitreal and periocular injections is often unable to prevent recurrences due to their short half-life. Since the emergence of intravitreal implants (Vitrasert, Retisert), it has become possible to circumvent these therapeutic challenges. A detailed review in the PubMed index yielded 155 articles, of which 22 were analyzed based on exclusion criteria. A recent shift from surgically sutured to minimally invasive injectable implants mainly indicated for noninfectious uveitis is evident from the literature. This review article also provides insights into dexamethasone (Ozurdex) and recent fluocinolone acetonide (Yutiq, Iluvien) implants with particular emphasis on their improved safety and efficacy. Dexamethasone implants favor the therapeutic goal of prevention of recurrences, whereas the use of fluocinolone implants helps to attain better visual outcomes due to their longer duration of action. Thus, the review provides recent literature supporting the role and indication of sustained release intravitreal implants in the management of noninfectious intermediate and posterior uveitis.

Transcription factor EGR2 alleviates autoimmune uveitis via activation of GDF15 to modulate the retinal microglial phenotype

Uveitis is a vision-threatening disease primarily driven by a dysregulated immune response, with retinal microglia playing a pivotal role in its progression. Although the transcription factor EGR2 is known to be closely associated with uveitis, including Vogt-Koyanagi-Harada disease and Behcet's disease, and is essential for maintaining the dynamic homeostasis of autoimmunity, its exact role in uveitis remains unclear. In this study, diminished EGR2 expression was observed in both retinal microglia from experimental autoimmune uveitis (EAU) mice and inflammation-induced human microglia cell line (HMC3). We constructed a mice model with conditional knockout of EGR2 in microglia and found that EGR2 deficiency resulted in increased intraocular inflammation. Meanwhile, EGR2 overexpression downregulated the expression of inflammatory cytokines as well as cell migration and proliferation in HMC3 cells. Next, RNA sequencing and ChIP-PCR results indicated that EGR2 directly bound to its downstream target growth differentiation factor 15 (GDF15) and further regulated GDF15 transcription. Furthermore, intravitreal injection of GDF15 recombinant protein was shown to ameliorate EAU progression in vivo. Meanwhile, knockdown of GDF15 reversed the phenotype of EGR2 overexpression-induced microglial inflammation in vitro. In summary, this study highlighted the protective role of the transcription factor EGR2 in AU by modulating the microglial phenotype. GFD15 was identified as a downstream target of EGR2, providing a unique target for uveitis treatment.

Administration of Nicotine Can Inhibit Myopic Growth in Animal Models.

While previously investigating the mechanism by which atropine inhibits ocular growth, we observed that stimulation of nicotinic receptors can inhibit experimental myopia. This study expands on that preliminary finding and investigates the safety and efficacy of nicotinic stimulation in the inhibition of ocular growth. Nicotine's ability to inhibit form-deprivation myopia (FDM), following intravitreal injection (9 chicks per group) or topical application (6 chicks per group), was investigated over three doses. The ability of nicotine to inhibit lens-induced myopia (LIM) was also tested (in 12 chicks). For ocular safety, following 4weeks of topical treatment with nicotine (n = 10), pupillary reflex, intraocular pressure, corneal curvature/thickness, lens thickness, retinal health (retinal thickness/cell apoptosis), as well as retinal function (electroretinogram recordings) were assessed. We also examined the effects of nicotine on non-ocular autonomic functions in both chicks (n = 5) and mice (n = 5). Nicotine was observed to significantly inhibit the development of FDM in chicks when administered as an intravitreal injection (P<0.05) or topical eye drops (P<0.05), albeit not in a dose-dependent manner. Nicotine also inhibited LIM (P<0.05) to a similar degree to that seen for FDM. Although ocular health was (for the most part) unaffected by nicotine, the highest topical dose induced a temporary reduction in cardiorespiratory output (P<0.05). Nicotine, administered as an intravitreal injection or topical eye drop, significantly inhibits the development of experimental myopia. Although the anti-myopic effects observed presently are interesting, the well-reported side effects (expanded on presently) and addictive properties of nicotine would preclude its clinical use.

Intravitreal injection practice patterns among Chinese ophthalmologists.

To describe the practice patterns of intravitreal injections (IVIs) among ophthalmologists in China. This was a cross-sectional online survey. Ophthalmologists who had performed accumulated more than 100 injections were contacted by the Brightness Center, a hospital-based national network, to complete an anonymous, 24-question, internet-based survey. They were surveyed on practices in injection techniques, pre-, and post-injections procedures. A total of 333 ophthalmologists from 28 provinces/municipalities/autonomous regions responded to the survey (50.68% response rate). The 91.29% of the respondents evaluated systemic risk factors by medical history, electrocardiogram (ECG) and blood test. All the respondents used pre-injection prophylactic antibiotics. Most checked intraocular pressure (IOP, 99.1%) and blood pressure (96.1%) before injections. A majority of the respondents performed injections in the operating room (98.8%), wore masks (99.7%), gloves (99.4%) and sterile surgical clothing (96.1%), performed topical anesthetics (97.9%), and applied povidone-iodine (95.8%) pre-injection. The 61.26% of the respondents dilated pupil. About half of the respondents (51.05%) performed bilateral injections in the same setting. Superior temporal quadrant (40.54%) was the most frequent site of injection. Around three quarters used 30-gauge needles. Most respondents (97.9%) measured the site of injection from limbus. More than half (53.45%) performed conjunctiva displacement prior to injection. The 32.43% of the respondents checked IOP post-injection and 87.99% physicians checked hand motion (HM) or counting fingers (CF) after injection, while 36.94% observed optic nerve perfusion. All participants used topical antibiotics post-injections. Most physicians (91.89%) reviewed patients on the following day. This study provides a description of the real-world practice patterns in IVIs in China and offers critical information regarding education and training of ophthalmologists and amendment of local society guidelines.

Impact of microorganism virulence on endophthalmitis outcomes

AimsTo determine the impact of microorganism virulence on visual outcomes in endophthalmitis.MethodsRetrospective, multicentre cohort study of patients presenting with endophthalmitis between 2006 and 2021. A literature review was conducted to...

Non-Pharmacological Aspects of Intravitreal Dexamethasone Implant Injections: A Retrospective Study of 3430 Injections and Complications.

This study aims to evaluate the non-pharmacological safety profile of intravitreal dexamethasone (DEX) implants in cases with different etiologies. This retrospective university-based study analyzed clinical reports of patients receiving 0.7 mg DEX implant injections between 2013 and 2023. The study recorded patient demographics, injection indications, and follow-up data. Complications caused by the injection procedure and adverse events other than pharmacological side effects within a 3-month period were included. In this study, 3430 DEX implant injections were made into 1471 eyes of 1091 patients. Non-pharmacological complications developed in 611 injections (17.8%). Subconjunctival hemorrhage was noted as the leading non-pharmacological complication (n=576, 16.8%). Sight-threatening 35 non-pharmacological adverse events and complications (1.0%) were recorded. Cases of anterior chamber migration, vitreous hemorrhage, retinal detachment, endophthalmitis, hypotony, and implant misplacement were observed. Cases requiring intensive treatments and additional surgical interventions were encountered. The injection of the DEX implant may lead to non-pharmacological complications caused by the mechanical impact of the injection or improper positioning of the implant, potentially resulting in vision loss. Severe outcomes such as corneal decompensation, retinal detachment, and endophthalmitis can ensue, emphasizing the gravity of these complications. Careful selection of patients and adherence to proper injection techniques are essential in reducing these risks.

Predictive Factors for Functional and Anatomical Outcomes After Anti-VEGF Treatment for Macular Edema in Patients with Branch Retinal Vein Occlusion.

This study aimed to identify predictive factors for the improvement of best-corrected visual acuity (BCVA) and reduction of central macular thickness (CMT) after treatment of macular edema (ME) due to branch retinal vein occlusion (BRVO) in a real-world setting. This retrospective study included patients with ME secondary to BRVO who were treated with intravitreal injection of bevacizumab as the first-line therapy and were followed up for 12 months. Demographic and clinical data, in addition to baseline spectral domain optical coherence tomography (SD-OCT) features, were considered as possible biomarkers of final BCVA and CMT. We also collected the data concerning the need for additional treatment including sectorial laser photocoagulation, change to another anti-VEGF agent, or intravitreal corticosteroid injection. A total of 161 eyes were analyzed. BCVA significantly improved from baseline to 12-month follow-up (0.6 and 0.4 logMAR, respectively; P 0.01). CMT decreased significantly during the follow-up period (from 498.0 to 325.0 m; P 0.01). Final BCVA correlated positively with baseline BCVA (P 0.01, r = 0.57). Older age at diagnosis and baseline SD-OCT findings including CMT, disruption of the retinal inner layers, retinal pigment epithelium (RPE) damage, and impairment of the ellipsoid zone and external limiting membrane negatively affected final BCVA (P 0.01). Multiple regression analysis identified age and BCVA at baseline as the only independent predictors of final BCVA (P = 0.001 and P 0.01, respectively). No association was found between clinical data, SD-OCT parameters, and final CMT. Various clinical and SD-OCT parameters are prognostically relevant for visual improvement in ME secondary to BRVO. Age at diagnosis and baseline BCVA were found to be independent predictors of visual outcome.

Treatment Options and Referral Pattern among Patients with Retinal Diseases Attending an Eye Clinic in a Tertiary institution, North Central Nigeria.

Objectives: The aim of the study was to determine the treatment modalities and pattern of referral of patients with retinal diseases in the eye clinic. Methods: All consenting new patients attending the eye clinic were recruited for the study and interviewed by the author. The treatment offered to the participants diagnosed with retinal disease (medical, surgical, LASER, optical or a combination) was recorded. Information on the patient’s referral for vitreoretinal consultation (this could be ‘yes’ or ‘no’) and reasons for the referral were also documented and analyzed. Results: treatment options for the 278 study participants were: medical for 100 (36%), optical for 94 (33.8%) optical correction, surgical for 24 (8.6%), LASER photocoagulation for 6 (2.2%) and a combination of LASER photocoagulation and intravitreal avastin injection for 20 (7.2%) patients. Counselling and watchful expectancy accounted for treatment of 34 (12.2%) patients. Seventy-four patients of the 278 included in the study had retinal diseases. Of these 74 with retinal diseases, 46 (62.2%) were referred to vitreoretinal units out of which 39 (84.8%) patients were referred to the vitreoretinal unit in JUTH and 7 (15.2%) were referred to vitreoretinal units elsewhere. The referrals were largely on account of unavailability of requisite equipment in 3 (42.8%) patients, surgical expertise in 2 (28.6%) patients and patient request in 2 (28.6%) cases. Conclusion: The need for establishment of standard vitreoretinal services strategically in each geo-political zone of Nigeria to cater more efficiently to the needs of patients with retinal diseases and appropriate referral cannot be overemphasized

Evaluation of Foveal Vasculature by Optical Coherence Tomography Angiography after Pan-Retinal Photocoagulation versus Intravitreal Anti-VEGF Injections.

This study aimed to compare macular vascular changes one and three months after treatment with either panretinal photocoagulation (PRP) or intravitreal bevacizumab (IVB). A total of 62 eyes with very severe non-proliferative diabetic retinopathy or early proliferative diabetic retinopathy without center-involved diabetic macular edema, were included in this retrospective study. Thirty-nine eyes were allocated to the PRP group, while 23 eyes were treated with IVB. Optical coherence tomography angiography (OCTA) was performed to measure foveal avascular zone (FAZ) characteristics as well as the densities of superficial and deep capillary plexuses (SCP and DCP). In the IVB group, the FAZ area and perimeter expanded at month one but returned to baseline level after three months. In the PRP group, however, the FAZ area and perimeter were rather steady. Changes in the FAZ area were significantly different between the treatment groups at month one (P = 0.02), but not at month three (P = 0.31). There was no significant difference in the change in FAZ circularity index between the two groups at each time point (P = 0.55 and P = 0.31). Similarly, changes in SCP density were not statistically significant between the two groups at both time points (all Ps 0.05). A comparison of the two treatment arms based on the mean change in DCP density revealed a significant difference at month one, but not at month three (P = 0.01 and P = 0.49, respectively). Although bevacizumab and PRP have different short-term macular vascular responses, both therapies have the ability to normalize or stabilize vascular measures over time.

Clinical Outcomes of Intravitreal Brolucizumab Injection for Refractory Neovascular Age-related Macular Degeneration

Purpose: To investigate the clinical outcomes and intraocular inflammation (IOI) following intravitreal brolucizumab injection for the treatment of refractory neovascular age-related macular degeneration (nAMD).Methods: This retrospective study reviewed the medical records of nAMD patients who received intravitreal brolucizumab injection that was switched from other anti-vascular endothelial growth factor (anti-VEGF) agents due to limited responses. The changes in subretinal/intraretinal fluid (SRF/IRF) and development of IOI were evaluated using slit lamp examination, fundoscopy, and optical coherence tomography.Results: The study included 76 eyes of 75 patients (56 males, 19 females). SRF and IRF disappeared in 55.3% (42/76 eyes) after the first injection and in 52.3% (23/44 eyes) of the remaining eyes after the third injection. The mean treatment interval increased from 5.6 to 9.6 weeks (&lt;i&gt;p&lt;/i&gt; &lt; 0.001). Visual acuity did not change. Eleven eyes (14.5%) developed IOI: an anterior chamber reaction in two eyes, vitritis in nine eyes, retinal vasculitis in one eye, and no retinal vascular occlusion. All IOI was treated with steroid eye solution or oral medication and recovered within 3.8 weeks. Three eyes also underwent subtenon steroid injection. Early recovery from IOI was observed in the subtenon steroid injection group (1.67 ± 0.58 vs. 4.63 ± 2.97 weeks, &lt;i&gt;p&lt;/i&gt; = 0.048). Visual acuity (logMAR) decreased from 0.51 to 0.67 when IOI developed (&lt;i&gt;p&lt;/i&gt; = 0.018), but increased to 0.52 after recovery from IOI.Conclusions: Approximately half of the eyes with refractory nAMD showed complete resolution of SRF/IRF when receiving brolucizumab. IOI had a high incidence, but recovery was successful, with careful monitoring and intensive steroid treatment.