Anti-vascular Endothelial Growth Factor Monotherapy Research Articles

Stable inhibition of choroidal neovascularization by adeno-associated virus 2/8-vectored bispecific molecules.

Neovascular age-related macular degeneration (nAMD) causes severe visual impairment. Pigment epithelium-derived factor (PEDF), soluble CD59 (sCD59), and soluble fms-like tyrosine kinase-1 (sFLT-1) are potential therapeutic agents for nAMD, which target angiogenesis and the complement system. Using the AAV2/8 vector, two bi-target gene therapy agents, AAV2/8-PEDF-P2A-sCD59 and AAV2/8-sFLT-1-P2A-sCD59, were generated, and their therapeutic efficacy was investigated in laser-induced choroidal neovascularization (CNV) and Vldlr-/- mouse models. After a single injection, AAV2/8-mediated gene expression was maintained at high levels in the retina for two months. Both AAV2/8-PEDF-P2A-sCD59 and AAV2/8-sFLT-1-P2A-sCD59 significantly reduced CNV development for an extended period without side effects and provided efficacy similar to two injections of current anti-vascular endothelial growth factor monotherapy. Mechanistically, these agents suppressed the extracellular signal-regulated kinase and nuclear factor-κB pathways, resulting in anti-angiogenic activity. This study demonstrated the safety and long-lasting effects of AAV2/8-PEDF-P2A-sCD59 and AAV2/8-sFLT-1-P2A-sCD59 in CNV treatment, providing a promising therapeutic strategy for nAMD.

Aqueous humour interleukin-6 and vision outcomes with anti-vascular endothelial growth factor therapy

BackgroundThis analysis evaluated aqueous humour (AH) interleukin (IL)-6 concentrations and the association between AH IL-6 and visual outcomes in patients with neovascular age-related macular degeneration (nAMD) or diabetic macular oedema (DMO) receiving anti–vascular endothelial growth factor (VEGF) monotherapy.MethodsPost hoc analysis of the multicentre, double-masked, randomised HARBOR (NCT00891735) and READ-3 (NCT01077401) trials. HARBOR enrolled treatment-naïve nAMD patients. READ-3 enrolled treatment-naïve/previously treated DMO patients. HARBOR patients received ranibizumab 0.5 or 2.0 mg monthly or as needed; AH samples were collected at month 2, after two previous intravitreal injections. READ-3 patients received ranibizumab 0.5 or 2.0 mg as needed; AH samples were collected at baseline and months 3, 6, 9, and 12. Main outcome measure: association between AH IL-6 concentrations and month 24 best-corrected visual acuity (BCVA).ResultsIn both trials (HARBOR, N = 36; READ-3, N = 137), patients with higher AH IL-6 concentrations had worse visual outcomes. HARBOR patients with low AH IL-6 concentrations at month 2 had a mean (95% CI) BCVA change at month 24 of +2.9 (−2.6, 8.3) letters, whereas patients with high AH concentrations had a mean (95% CI) BCVA change of −9.0 (−22.7, 4.7) letters. READ-3 patients with low AH concentrations at baseline had a mean (95% CI) BCVA change at month 12 of +9.3 (7.4, 11.3) letters, whereas patients with high AH concentrations had a mean (95% CI) BCVA change of +5.6 (2.2, 9.1) letters.ConclusionsHigher IL-6 AH concentrations may predict suboptimal visual responses to anti–VEGF monotherapy in patients with nAMD/DMO.

Intravitreal anti-vascular endothelial growth factor and combined photodynamic therapy for pachychoroid neovasculopathy: long-term treatment outcomes

PurposeTo examine the long-term visual outcomes after initial treatment with combined photodynamic therapy (PDT) or aflibercept treat-and-extend (TAE) monotherapy in patients with pachychoroid neovasculopathy (PNV).MethodsPatients diagnosed with PNV, initially treated with PDT combined with anti-vascular endothelial growth factor (VEGF) or intravitreal aflibercept (IVA) monotherapy in the TAE protocol and followed up for at least 6 months, were included in the study. Medical records were retrospectively reviewed. Survival analysis was performed, in which deterioration in logMAR visual acuity by 0.1 or 0.3 is defined as “death.” The annual number of treatments was also analyzed. Sub-analysis was performed on 33 patients diagnosed with PNV without polypoidal lesions.ResultsThis study included 46 patients (23 in the initial combined PDT group and 23 in the IVA TAE group). Mean age, sex, mean baseline logMAR visual acuity, or duration of observation (3.6 ± 3.2 years vs. 3.1 ± 1.9 years) in both groups were comparable. As for visual outcome, no significant differences were found in survival analysis based on worsening of 0.1 or 0.3 logMAR (3-year survival; 26% vs. 26%, 91% vs. 90%, respectively). Meanwhile, the additional number of anti-VEGF injections per year was significantly lower in the initial combined PDT group than in the IVA TAE group (1.0 ± 1.3 vs. 4.1 ± 1.5, p < 0.0001). No significant differences were found in the number of additional PDTs per year (0.07 ± 0.20 vs. 0.02 ± 0.09, p = 0.27). Similar results were found in a sub-analysis of 33 patients without polyps.ConclusionIn the treatment of PNV, regardless of the presence of polyps, the long-term visual outcomes were similar between the initial combined PDT and IVA TAE monotherapy. However, the annual number of anti-VEGF injections was lower in the initial combined PDT group than in the aflibercept TAE group, whereas that of PDT was comparable.

Outcomes in the Treatment of Subretinal Macular Hemorrhage Secondary to Age-Related Macular Degeneration: A Systematic Review.

Background: Subretinal macular hemorrhage (SRMH) secondary to age-related macular degeneration (AMD) is a relatively rare condition in ophthalmology characterized by blood collection between the neurosensory retina and the retinal pigment epithelium (RPE). Without prompt treatment, visual prognosis is poor. A plethora of treatment approaches have been tried over the past years ranging from intravitreal anti-vascular endothelial growth factor (anti-VEGF) monotherapy to direct subretinal surgery, with no conclusive superiority of one over the other. Materials and Methods: We conducted a systematic review of the outcomes and treatment modalities of SRMH from inception to 14 June 2022, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). The level of evidence was assessed for all included articles according to the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Results: A total of 2745 articles were initially extracted, out of which 1654 articles were obtained after duplicates were removed and their abstracts screened. A total of 155 articles were included for full-text review. Finally, 81 articles remained that fulfilled the inclusion criteria. Conclusions: Even though there are solid results supporting a variety of treatments for SRMH, the best treatment modality has still not been conclusively demonstrated and further research is needed.

FLUORESCEIN ANGIOGRAPHY EVALUATION OF CHILDREN PREVIOUSLY TREATED WITH ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR MONOTHERAPY FOR RETINOPATHY OF PREMATURITY.

To determine the level of vascularization and peripheral vascular findings by fluorescence angiography in patients with aggressive retinopathy of prematurity or Type 1 retinopathy of prematurity treated with a single dose of anti-vascular endothelial growth factor. Data of patients referred to the authors' clinic for fluorescence angiography examination between June 2016 and September 2021 were retrospectively analyzed. Patients who had their first fluorescence angiography examination at the age of 1 year or older were included in the study. A total of 486 eyes of 250 patients were included. Of these, 83 eyes (17.1%) had vascular termination in Zone II and 403 eyes (82.9%) in Zone III. In 62.7% of eyes, the distance from the vascular terminals to the temporal ora serrata was less than two disk diameters, and in 20.2%, it was more than two disk diameters. Abnormal vascular findings were noted, including circumferential vessels (41.2%), finger-like projection anomaly (36.2%), hyperfluorescence (16.9%), fine branching and blunt termination (15%), and arteriovenous shunt (9.9%). Fluorescence angiography performed late in the course of treatment can clearly define the vascular termini and detect abnormalities that cannot be detected by indirect ophthalmoscopy. Follow-up with fluorescence angiography can help prevent complications that can lead to vision loss.

Refractive errors in infants with retinopathy of prematurity treated using laser or anti-vascular endothelial growth factor monotherapy

Background: Infants treated for retinopathy of prematurity (ROP) could develop visually significant refractive errors. In this study, we report pre-treatment refractive errors in premature infants with treatment-requiring ROP treated using laser or anti-VEGF monotherapy and compare the components of post-treatment refractive error values between the two treatment groups at different follow-up timepoints.&#x0D; Methods: In this retrospective cohort study, we analyzed 360 eyes of 181 premature infants with treatment-requiring ROP who were referred to Farabi Eye Hospital, Tehran, Iran between March 2020 and April 2021. Of the 360 eyes, 195 received laser monotherapy (laser treatment group) and 165 received an intravitreal anti-VEGF injection (anti-VEGF therapy group). All included eyes underwent pre- and post-treatment cycloplegic refraction. Cycloplegia was induced for each infant by instilling a mixed eye drop containing 1% tropicamide, 2.5% phenylephrine, and 0.5% tetracaine (in equal volumes) in each eye three times at five-minute intervals. Cycloplegic refraction was performed 30 minutes after the third instillation.&#x0D; Results: The mean (standard deviation [SD]) gestational age (GA) and birth weight (BW) of the infants were 29.0 (2.0) weeks and 1241.0 (403.0) g, respectively. The male-to-female ratio in the entire study cohort was 107 (59.1%) / 74 (40.9%), whereas the ratios in the anti-VEGF therapy group and laser treatment group were 47 (56.6%) / 36 (43.4%) and 60 (61.2%) / 38 (38.8%), respectively. The pre-treatment assessment revealed that 218 (60.6%) eyes were hyperopic, 112 (31.1%) were myopic, and 30 (8.3%) were emmetropic. In the anti-VEGF therapy group, 87 (52.7%) eyes were hyperopic, 63 (38.2%) were myopic, and 15 (9.1%) were emmetropic. In the laser treatment group, 131 (67.2%) eyes were hyperopic, 49 (25.1%) were myopic, and 15 (7.7%) were emmetropic. The mean (SD) spherical refractive error and spherical equivalent of refractive error (SEQ) at the 1-week, 1-month, and &gt; 6-month post-treatment follow-up timepoints; the mean cylindrical refractive error at the 3-month post-treatment timepoint; and the mean SEQ at the time of ROP regression were significantly different between the treatment groups (all P &lt; 0.05). The rate of anisometropia increased significantly from 3.4% at baseline to 9.2% at the 6-month post-treatment follow-up timepoint (P &lt; 0.05).&#x0D; Conclusions: In this study, the most common pre-treatment refractive status of all included eyes with treatment-requiring ROP and eyes in each treatment group was hyperopia, followed by myopia and emmetropia. At the more than 6-month post-treatment follow-up, cycloplegic refraction revealed that the laser-treated eyes were significantly more hyperopic than the anti-VEGF-treated eyes, a finding similar to the pre-treatment refraction results. Further studies of same cohort with a longer follow-up period and a control group are needed to determine the real-world effect of each treatment modality on the refractive statuses of children treated for ROP.

Intravitreal anti-vascular endothelial growth factor monotherapy in age-related macular degeneration with submacular hemorrhage

The purpose of this study was to evaluate the 1-year visual outcomes of patients treated with intravitreal aflibercept (IVA) or brolucizumab (IVBr) for submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (AMD). We retrospectively studied 62 treatment-naïve eyes with SMHs exceeding one disc area (DA) secondary to AMD treated with IVA or IVBr. All patients received three monthly intravitreal injections in the loading phase followed by as-needed injections or fixed dosing. If a vitreous hemorrhage (VH) developed during the follow-up period, injections were discontinued and vitrectomy was performed. We evaluated the changes in the best-corrected visual acuity (BCVA) and factors that affected the BCVA improvement and VH development. A VH during treatment developed in five eyes (8.1%) (VH + group), and the mean BCVA worsened from 0.45 to 0.92. The BCVA improved significantly (P = 0.040) in the remaining 57 eyes (VH − group) from 0.42 to 0.36. The development of VHs was associated with significantly (P < 0.001) less VA improvement. Furthermore, large DAs and younger age at baseline were associated significantly (P = 0.010 and 0.046, respectively) with the development of VHs. Both IVA and IVBr appeared to improve functional outcomes in patients with SMH secondary to AMD when VHs did not develop. However, a VH developed in 8.1% of eyes after treatment. Although anti-vascular endothelial growth factor treatments were well-tolerated, for cases with large SMH at baseline, it should be considered that VH may occur during the monotherapy treatment process using IVA or IVBr, and that achieving good visual outcomes may be difficult in some cases.

Polypoidal Choroidal Vasculopathy: An Update on Diagnosis and Treatment

Polypoidal choroidal vasculopathy (PCV) is a vascular disease of the choroid that leads to hemorrhagic and exudative macular degeneration. It may cause significant vision loss and thus affect the quality-of-life and psychological well-being. Non-invasive, non-ICGA-based OCT criteria have shown reliable results to plan adjunct photodynamic therapy (PDT) treatment, with the complete and consistent coverage of polypoidal lesions (PL) and branching neovascular network (BNN). The safety and efficacy of anti-vascular endothelial growth factor (anti-VEGF) monotherapy and its combination with verteporfin PDT have been established. However, treatment is still challenging due to frequent follow-ups, non-availability of PDT, and need for multiple anti-VEGF injection visits that increase the treatment burden and lead to patients being lost to follow-up. Effective treatments that prolong intervals between injections while maintaining vision and anatomical gains remain a critical unmet need. Longer acting molecules, like brolucizumab, have shown non-inferiority in BCVA gains and superior anatomical outcomes compared to other anti-VEGF agents. Newer therapies in the pipeline to enhance the efficacy and longevity of treatment include Faricimab and a port delivery system (PDS). This review summarizes the most recent diagnostic and treatment approaches in PCV to offer better treatment avenues.

Pars plana vitrectomy and subretinal tissue plasminogen activator for large exudative submacular hemorrhage: a case series

BackgroundTo evaluate anatomical and functional outcomes of patients with large submacular hemorrhage (SMH) who treated by pars plana vitrectomy (PPV) in combination with subretinal tissue plasminogen activator (TPA) injection, intraocular gas tamponade, and with additional post-operative interventions.MethodsMedical records of 9 patients who presented with large SMH secondary to age-related macular degeneration (AMD) and underwent PPV, subretinal TPA injection, and gas tamponade at Chiang Mai university hospital between January 2012 and January 2020 were reviewed. Collected data included preoperative visual acuity (VA), SMH extent and duration, intraoperation and post-operation complications, post-operative anatomical and VA responses, and the need for administer post-operation additional treatments.ResultsOverall, five patients were male and four patients were female with a mean (SD) age of 66.9 (7.7) years and a mean (SD) follow-up of 21.1 (16.1) months. A mean (SD) duration of SMH was 15.1 (10.9) days with a mean (SD) extent of SMH was 6.2 (3.4) disc diameters. At 1-month post-operation, complete SMH displacement was noted in eight (88.9%) patients. The mean (SD) VA significantly improved from LogMAR 1.9 (0.4) to 1.1 (0.4), (P = 0.004). During follow-up, eight patients (88.9%) were given additional therapy (anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy, or in combination). At final follow-up, a mean (SD) LogMAR VA of 0.9 (0.4) was significantly improved compared to baseline (P = 0.004). For intra- and post-operation complications, none developed intraoperative retinal break and retinal detachment.ConclusionsVitrectomy with subretinal TPA injection, intraocular gas tamponade, and additional post-operation treatments provide benefit for anatomical and visual outcomes for patients with large SMH. It may consider as one of effective treatment in this group of patients.

Progression of Polypoidal Lesions Associated with Exudative Recurrence in Polypoidal Choroidal Vasculopathy

To investigate the characteristics of the branching vascular network (BVN) and polypoidal lesions in polypoidal choroidal vasculopathy (PCV) to determine near-term indicators that may predict exudative recurrence. Retrospective cohort study. Patients with PCV receiving anti-vascular endothelial growth factor (VEGF) monotherapy or anti-VEGF plus photodynamic therapy were followed for at least 1 year using swept-source OCT angiography (SS-OCTA) imaging. Patients were divided into 2 groups based on whether exudative recurrence occurred during follow-up. Multiple parameters were collected and compared between the 2 groups, such as age, gender, visual acuity, number of polypoidal lesions, lesion area at the first SS-OCTA visit, and total lesion area change from the first SS-OCTA visit to the last SS-OCTA visit. To evaluate the association between SS-OCTA imaging-based risk factors and the exudative recurrences, imaging features associated with PCV such as BVN growth and polypoidal lesion progression (enlargement, new appearance, and reappearance) at each follow-up visit were analyzed. The time intervals from the nonexudative visit with lesion progression to the corresponding exudative recurrence visit were documented to explore their association with exudative recurrences. Cox regression and logistic regression analyses were used. Association between BVN growth and polypoidal lesion progression with exudative recurrence. Thirty-one eyes of 31 patients (61% men) were included. Sixteen eyes had no recurrence of exudation, and 15 eyes had recurrence during follow-up. The average follow-up duration was 20.55 ± 6.86 months (range, 12-36 months). Overall, the recurrence group had worse best-corrected visual acuity (P= 0.019) and a greater increase in lesion area (P= 0.010). Logistical regression analysis showed that polypoidal lesion progression, including new appearance, enlargement, and reappearance of polypoidal lesions, was associated with exudative recurrences within 3 months (odds ratio, 26.67, 95% confidence interval, 3.77-188.54, P= 0.001). Growth of nonexudative BVN and progression of polypoidal lesions were found to be lesion characteristics associated with exudative recurrences, and progression of polypoidal lesions might serve as a stand-alone indicator for the near-term onset of exudation. In PCV, more frequent follow-up visits are recommended when polypoidal lesions show progression.

Comparison of treatment methods for submacular hemorrhage in neovascular age-related macular degeneration: conservative versus active surgical strategy

The optimal treatment of submacular hemorrhage (SMH) following neovascular age-related macular degeneration (nAMD) is controversial. This study aimed to compare visual outcomes of conservative versus active surgical treatment. Two hundred thirty-six eyes of 236 patients with SMH (≥ 1 disc diameter) were stratified into four groups: observation (n = 21); anti-vascular endothelial growth factor (VEGF) monotherapy (n = 161); non-surgical gas tamponade (n = 31); and subretinal surgery (n = 23). The primary outcome was best-corrected visual acuity (BCVA) at 12 months. The baseline BCVAs of the observation, anti-VEGF monotherapy, non-surgical gas tamponade, and subretinal surgery groups were 1.50 ± 0.70, 1.09 ± 0.70, 1.31 ± 0.83, and 1.62 ± 0.77 logarithm of minimal angle resolution (LogMAR), respectively. The mean BCVAs at 12 months were 1.39 ± 0.84, 0.90 ± 0.83, 1.35 ± 0.88, and 1.44 ± 0.91 LogMAR, respectively. After adjusting for age, baseline BCVA, SMH size, and the number of intravitreal anti-VEGF injections before SMH, the mean BCVA showed no significant difference among treatments at 12 months (P = 0.204). The anti-VEGF monotherapy group showed better mean BCVA significantly at 3 months (P < 0.001). Only baseline BCVA was associated with VA gain at 12 months (Odds ratio = 3.53, P < 0.001). This study demonstrated that there was no difference in 12 month visual outcomes among treatments and a better early visual outcome can be expected with anti-VEGF monotherapy.

Ethnic differences on long term outcomes of polypoidal choroidal vasculopathy after predominantly bevacizumab monotherapy

BackgroundA 3-year single-centre, retrospective, comparative, non-randomized cohort study to describe the long-term outcomes of treatment-naïve, Caucasian and non-Caucasian eyes with polypoidal choroidal vasculopathy (PCV) after treatment with predominantly Bevacizumab monotherapy or in combination with rescue photodynamic therapy (PDT).MethodsDemographics, visual outcomes, optical coherence tomography (OCT) and treatment data were collected up to 3 years after the first visit. Stratified analysis according to ethnicity and baseline vision was performed to identify factors predictive of long-term visual improvement and maintenance.ResultsA total of 89 eyes with PCV were identified, of which 14 received rescue verteporfin PDT. There was an equal distribution between Caucasian and non-Caucasian individuals. Non-Caucasians present at a younger age (67.3 vs. 76.0 years, p = 0.002), have a higher proportion of foveal involvement (80.9%, vs.54.2% p = 0.007), choroidal hyperpermeability (50% vs 25.8%, p = 0.013) and lower baseline visual acuity (53.1 vs. 63.3 letters, p = 0.008). Mean visual acuity (VA) gain was + 8.9 letters and + 5.0 letters at 1 and 3 years of follow-up, respectively. Non-Caucasian individuals had a lower mean final visual acuity (VA) (54.7 vs. 70.5, respectively; P < 0.001) and net gain in VA (+ 2.0 vs. + 7.6 letters, p = 0.581) compared to Caucasian individuals. The mean total number of injections given over 3 years was 14.ConclusionsMost patients treated with predominantly Bevacizumab anti-vascular endothelial growth factor (VEGF) monotherapy achieved sustained visual acuity gains out to 3 years. Due to ethnic-specific differences in presenting PCV phenotypes, non-Caucasians presented with lower baseline VA and had poorer long-term visual outcomes.

Rescue photodynamic therapy for age-related macular degeneration refractory to anti-vascular endothelial growth factor monotherapy

BackgroundTo evaluate the 3-year outcome in eyes with neovascular age-related macular degeneration (nAMD) treated with intravitreal anti-vascular endothelial growth factor monotherapy or rescue therapy using standard verteporfin photodynamic therapy (PDT), and corroborate efficacy of rescue PDT. MethodsPatients were administered aflibercept injections once a month for 3 months followed by once every 2 months in the first year. After year 1, treatment with aflibercept monotherapy as indicated or in combination with PDT at the retinal specialist's discretion. Only cases completing the three-year follow-up were included. Regression analysis with visual acuity and macular atrophy at year 3 was performed for the dependent variable. ResultsOf the 292 eyes, 15 eyes underwent rescue PDT following year 1. The best-corrected visual acuity (logarithm of minimal angle of resolution, mean/Snellen equivalent ± SD) was 0.35 (20/45) ± 0.38, 0.23 (20/30) ± 0.36, 0.26 (20/35) ± 0.38, and 0.31 (20/40) ± 0.42 at baseline, year 1, year 2, and year 3, respectively. Multiple regression analysis revealed that the rescue PDT was significantly associated with macular atrophy and poor visual outcome at year 3 (odds ratio = 1.2, p < 0.001; β = 0.23, p = 0.0029, respectively). ConclusionsThe visual outcome in eyes with nAMD retained baseline levels at year 3; however, patients treated with rescue PDT developed macular atrophy more frequently and poor visual outcomes.

Real world experience of the treatment outcome between photodynamic therapy combined with ranibizumab and aflibercept monotherapy in polypoidal choroidal vasculopathy

To provide real-world experiences of treating polypoidal choroidal vasculopathy (PCV) patients with photodynamic therapy (PDT) plus intravitreal injection of ranibizumab or intravitreal injection of aflibercept alone. Retrospective chart review of patients with PCV in a single tertiary referral center in Taiwan. Chart review of PCV patients treated with PDT and injection of ranibizumab or injection of aflibercept. A total of 101 eyes of 101 patients (38 females and 63 males) were reviewed. Of those, 48 and 53 eyes received primary/adjunctive PDT along with injections of ranibizumab or intravitreal injections of aflibercept only, respectively. Initial visual acuity (VA) and central subfield choroidal thickness were similar between the two groups (p > 0.05). In addition, changes in VA at 3, 6, and 12 months post treatment were similar. The central retinal thickness decreased with either treatment (p < 0.01); however, this change did not translate into VA performance (p > 0.05). In the subgroup analysis of pachychoroid and non-pachychoroid patients, better initial VA and post-treatment VA at 3 months and 6 months was noted in the latter group of patients treated with anti-vascular endothelial growth factor monotherapy (p < 0.05). Aflibercept monotherapy is comparable with PDT plus ranibizumab in PCV patients with PCV (pachychoroid and non-pachychoroid patients). In addition, better prognosis regarding VA was observed in non-pachychoroid patients treated with aflibercept monotherapy.

Real-world outcomes of combined therapy of photodynamic therapy with anti-vascular endothelial growth factor for polypoidal choroidal vasculopathy

ObjectivesTo describe the real-world outcomes of photodynamic therapy (PDT) as a rescue therapy in eyes with polypoidal choroidal vasculopathy (PCV) refractory to anti-vascular endothelial growth factor (VEGF) monotherapy in a British cohort of patients.MethodsThis is a retrospective chart review of 53 eyes with PCV. Based on the timing of PDT, the eyes were stratified into two groups (9 in the Initial-PDT group, 44 in the Deferred group). The number of anti-VEGF injections/year and the best corrected visual acuity (BCVA) before and after PDT were analysed. Multivariate regression model was created to identify factors predictive of visual outcome and treatment burden after PDT.ResultsThe Deferred group received a mean of 9.4 injections/year but significantly reduced to 7.2 after PDT (p < 0.001). The Initial-PDT group required significantly fewer injections after PDT compared to the Deferred group (p = 0.004). The Deferred group experienced improvement in BCVA from 58.7 letters at baseline to 63.8 at 18-months follow-up (p < 0.001), but no significant increase was observed in the Initial-PDT group (p = 0.310). Better baseline BCVA is associated with higher likelihood of achieving good BCVA ≥ 70 letters after PDT (Odd Ratio=1.12, 95% CI: 1.03–1.21, p = 0.006), while increased number of anti-VEGF injections/year before PDT reduces the likelihood of easing treatment burden to ≥12 weeks apart between each injection after PDT (Odd Ratio=0.724, 95% CI: 0.58–0.91, p = 0.006).ConclusionsPDT as a rescue therapy is beneficial in the long-term management of PCV, particularly in eyes that had experienced a significant period of prior exposure to anti-VEGF monotherapy.

Addition of photodynamic therapy to anti-vascular endothelial growth factor drugs compared to anti-vascular endothelial growth factor monotherapy for polypoidal choroidal vasculopathy.

Polypoidal choroidal vasculopathy is characterized by multiple and recurrent serosanguineous detachments of the retinal pigment epithelium and aneurysmal protrusions in the choroidal vessels. Different therapeutic options have been proposed, including anti-vascular endothelial growth factor drugs and photodynamic therapy. Controversy exists as to whether combination therapy is superior to anti-vascular endothelial factor drugs alone. We searched Epistemonikos, the largest database of systematic reviews in health, maintained by screening multiple sources of information, including MEDLINE/PubMed, EMBASE, and Cochrane. We extracted data from the identified reviews, analyzed the data from the primary studies, performed a meta-analysis, and prepared a summary table of the results using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method. We identified three systematic reviews that together included twelve primary studies. Of these, two were randomized trials, and only one of them was included in the analysis. The addition of photodynamic therapy may result in little or no difference in the incidence of retinal hemorrhage and visual acuity gain at six months (low certainty of evidence). On the other hand, the combination of photodynamic therapy and anti-vascular endothelial growth factor drugs compared to anti-vascular endothelial growth factor alone is likely to increase polyp regression at three and six months and reduce central retinal thickness at six months.

Pachychoroid-phenotype effects on 5-year visual outcomes of anti-VEGF monotherapy in polypoidal choroidal vasculopathy.

To investigate whether the efficacy of anti-vascular endothelial growth factor (VEGF) monotherapy for polypoidal choroidal vasculopathy (PCV) differs between pachychoroid and non-pachychoroid phenotypes in the long term. This retrospective longitudinal study included 115 treatment-naïve eyes in 115 consecutive patients with symptomatic PCV who were treated with anti-VEGF monotherapy and were followed up for 5 years. Eligible eyes were assigned to either a pachy-PCV group, with a pachychoroid phenotype, or a non-pachy-PCV group, without a pachychoroid phenotype. Best-corrected visual acuity (BCVA) and other parameters over a 5-year period were compared between the groups. Forty-eight eyes and 67 eyes were classified into the pachy-PCV and non-pachy-PCV groups respectively. Baseline and 5-year BCVA (logarithm of the minimum angle of resolution) were 0.19 ± 0.20 and 0.16 ± 0.28 in the pachy-PCV group, respectively, and 0.25 ± 0.26 and 0.26 ± 0.36 in the non-pachy-PCV group respectively. BCVA did not change significantly in either group (p = 0.18 and 0.08 respectively). BCVA did not differ between the groups at any observation time-point. Subfoveal choroidal thickness (SFCT) at baseline and at 5 years was significantly higher in the pachy-PCV group than in the non-pachy-PCV group (both p < 0.001); however, the mean rate of decrease in SFCT did not differ in either group over the 5-year period (22% vs. 23%, p = 0.81). Our findings suggest that anti-VEGF monotherapy was similarly effective for pachychoroid- and non-pachychoroid-phenotype eyes with PCV, for at least 5 years, although further studies are required.

THE INCIDENCE, CHARACTERISTICS, MANAGEMENT, PROGNOSIS, AND CLASSIFICATION OF BREAKTHROUGH VITREOUS HEMORRHAGE SECONDARY TO POLYPOIDAL CHOROIDAL VASCULOPATHY.

To describe breakthrough vitreous hemorrhage secondary to polypoidal choroidal vasculopathy (PCV). Patients with the diagnosis of PCV from January 2005 to March 2020 at Peking Union Medical College Hospital were retrospectively reviewed, cases with breakthrough vitreous hemorrhage were analyzed. Subgroup analysis was conducted regarding pachychoroid PCV and nonpachychoroid PCV. Among 722 PCV patients (834 eyes), 103 eyes with breakthrough vitreous hemorrhage (12.4%) were included. Pars plana vitrectomy and proper further interventions could significantly improve the best-corrected visual acuity from logMAR 2.15 ± 0.48 (Snellen 20/2825) to 1.65 ± 0.67 (20/893). Hemorrhagic retinal detachment, baseline central macular thickness, and best-corrected visual acuity were factors associated with final best-corrected visual acuity (P < 0.05). In the pachychoroid PCV group, patients were younger, all had hemorrhagic pigment epithelial detachment, with a higher prevalence of choroidal vascular hyperpermeability and hemorrhagic retinal detachment, thicker subfoveal choroidal thickness, and thinner central macular thickness; besides, the initial pars plana vitrectomy were more complicated, more additional surgeries had to be performed. More eyes in the nonpachychoroid PCV group had received anti-vascular endothelial growth factor or photodynamic therapy, mostly fibrovascular pigment epithelial detachment, the best-corrected visual acuity and the status of the fellow eye were significantly worse. For the final ocular status, more eyes in nonpachychoroid PCV group were taking anti-vascular endothelial growth factor monotherapy, whereas more eyes in pachychoroid PCV group were stable. The choroidal parameters of these two groups were all significantly different. Breakthrough vitreous hemorrhage is a troublesome complication of PCV. Pars plana vitrectomy and additional interventions are required for better prognosis. Vitreous hemorrhage secondary to pachychoroid PCV or nonpachychoroid PCV have different characteristics and prognosis.

Clinical features of pachyvessels associated with polypoidal choroidal vasculopathy in chronic central serous chorioretinopathy

To investigate the association between clinical features of chronic central serous chorioretinopathy (CSC) and subsequent development of polypoidal choroidal vasculopathy (PCV). Characteristics and treatment response of PCV secondary to CSC were described. This retrospective observational study included 18 patients with chronic CSC (18 eyes) with subsequent PCV and 36 controls (36 eyes) with chronic CSC without PCV development during follow-up. Clinical features were compared between the two groups. A logistic regression model was used to evaluate the risk factor of PCV formation. Treatments for PCV included anti-vascular endothelial growth factor (VEGF) monotherapy, photodynamic therapy (PDT), or PDT and anti-VEGF combination treatment. Subretinal fluid on optical coherence tomography images were assessed after treatments. Significant between-group differences were observed in best-corrected visual acuity after disease resolution and presence of pachyvessels (P = .001 and P = .003, respectively). The presence of pachyvessels in chronic CSC was associated with subsequent PCV (odds ratio = 6.00; 95% CI, 1.74–20.68; P = .005). CSC recurrence and subfoveal choroidal thickness (SFCT) were not significantly associated with subsequent PCV development (P = .393 and P = .911, respectively). The mean age of PCV diagnosis was 51 years, and the mean time from CSC diagnosis to PCV confirmation was 77.8 months. The mean (range) SFCT of PCV was 327.7 (134–599) μm. Nine patients received anti-VEGF monotherapy and 5 had disease remission. Four patients received PDT and anti-VEGF combination treatment and all of the 4 had disease remission. In chronic CSC, pachyvessel characteristics are associated with subsequent PCV development. This result will assist clinicians to evaluate CSC in clinical practice and provide insights into the pathogenesis of PCV.

Non-ICGA treatment criteria for Suboptimal Anti-VEGF Response for Polypoidal Choroidal Vasculopathy: APOIS PCV Workgroup Report 2

To develop and validate OCT and color fundus photography (CFP) criteria in differentiating polypoidal choroidal vasculopathy (PCV) from typical neovascular age-related macular degeneration (nAMD) in eyes with suboptimal response to anti-vascular endothelial growth factor (VEGF) monotherapy and to determine whether OCT alone can be used to guide photodynamic therapy (PDT) treatment. Clinical study evaluating diagnostic accuracy. Patients with nAMD who received 3-month anti-VEGF monotherapy but had persistent activity defined as subretinal fluid or intraretinal fluid at month 3 assessments. In phase 1, international retina experts evaluated OCT and CFP of eyes with nAMD to identify the presence or absence of features due to PCV. The performance of individual and combinations of these features were compared with ICGA. In phase 2, these criteria were applied to an independent image set to assess generalizability. In a separate exercise, retinal experts drew proposed PDT treatment spots using only OCT and near-infrared (NIR) images in eyes with PCV and persistent activity. The location and size of proposed spot were compared with ICGA to determine the extent of coverage of polypoidal lesions (PLs) and branching neovascular network (BNN). Sensitivity and specificity of CFP and OCT criteria to differentiate PCV from nAMD and accuracy of coverage of OCT-guided PDT compared with ICGA. In eyes with persistent activity, the combination of 3 non-ICGA-based criteria (sharp-peaked pigment epithelial detachment [PED], subretinal pigment epithelium [RPE] ring-like lesion, and orange nodule) to detect PCV showed good agreement compared with ICGA, with an area under the receiver operating characteristic curve of 0.85. Validation using both an independent image set and assessors achieved an accuracy of 0.77. Compared with ICGA, the OCT-guided PDT treatment spot covered 100% of PL and 90% of the BNN. In nAMD eyes with persistent activity, OCT and CFP can differentiate PCV from typical nAMD, which may allow the option of adjunct PDT treatment. Furthermore, OCT alone can be used to plan adjunct PDT treatment without the need for ICGA, with consistent and complete coverage of PL.