Macular neovascularization in inherited retinal diseases: A review.

Inherited retinal diseases (IRDs) are the most common cause of blindness in working-age adults. Macular neovascularization (MNV) may be a presenting feature or occurs as a late-stage complication in several IRDs. We performed an extensive literature review on MNV associated with IRDs. MNV is a well-known complication of Sorsby fundus dystrophy and pseudoxanthoma elasticum. Those with late-onset Stargardt disease may masquerade as exudative age-related macular degeneration (AMD) when MNV is the presenting feature. Peripherinopathies may develop MNV that responds well to a short course of anti-vascular endothelial growth factor (anti-VEGF) therapy, while bestrophinopathies tend to develop MNV in the early stages of the disease without vision loss. Enhanced S-cone syndrome manifests type 3 MNV that typically regresses into a subfoveal fibrotic nodule. MNV is only a rare complication in choroideraemia and rod-cone dystrophies. Most IRD-related MNVs exhibit a favorable visual prognosis requiring less intensive regimens of anti-vascular endothelial growth factor therapy compared to age-related macular degeneration. We discuss the role of key imaging modalities in the diagnosis of MNV across a wide spectrum of IRDs and highlight the gaps in our knowledge with respect to the natural history and prognosis to pave the way for future directions of research.

Clinical feature of cystoid macular degeneration in central serous chorioretinopathy.

Purpose: Cystoid macular degeneration (CMD) is a feature of chronic central serous chorioretinopathy (CSCR). Present study intended to analyze the clinical presentation, risk factors, choroidal features, and outcome of CMD in CSCR. Methods: This was a retrospective, record-based descriptive study, which included chronic CSCR eyes with CMD. Demographic profile and clinical history were obtained from medical records. Spectralis spectral domain optical coherence tomography (SDOCT; Heidelberg Engineering,Germany) was used for acquiring SDOCT images and for performing fluorescein angiography , indocyanine green angiography , and optical coherence tomography (OCT) angiography. Results: The study included 101 eyes of 69 consecutive patients of CSCR having CMD. The mean age of patients was 56 ± 9.4 years (range 40-79 years), and majority (63, 91.3%) of the patients were male. Prior history of corticosteroid use was present in seven (10.1%) patients. Mean time interval between the first diagnosis of CSCR and appearance of CMD was 55.3 ± 33.9 months. CMD was located away from the fovea in majority of eyes (68, 67.3%). Mean subfoveal choroidal thickness was 396.71 ± 90.5 µm. Subretinal pigment epithelium choroidal neovascularization was noted in four (3.96%) eyes. Conclusion: CMD appears as a late complication of CSCR and is usually present away from the fovea. Such eyes had thickened choroid and fewer cases had associated choroidal neovascularization. Further comparative studies would be needed to validate these findings.

CLINICAL ASSOCIATIONS AND PROGNOSTIC IMPLICATIONS OF REPAIR TISSUE PROLIFERATION IN EYES WITH RETINAL PIGMENT EPITHELIUM TEARS.

PURPOSE: To investigate demographic and clinical factors influencing the longitudinal changes of retinal pigment epithelium (RPE) dehiscence area after RPE tears, including the presence of RPE tear-associated repair proliferation (TARP), and identify factors associated with TARP development over follow-up. METHODS: Retrospective, single-center, observational cohort study of patients with a history of macular neovascularization and RPE tear. The area of RPE dehiscence was measured on repeated short-wavelength fundus autofluorescence imaging. Associations between covariates and RPE dehiscence areas were tested with multivariable linear mixed models. Associations between TARP development and clinical variables were investigated with Cox regression models. Factors associated with visual acuity changing rates were explored with linear mixed models. RESULTS: Thirty-seven eyes of 36 patients were included in this study and followed for a median time of 18 months. Tear-associated repair proliferation was identified in 27 eyes (73%). The median time for TARP detection was 112 days; none of the investigated factors was significantly associated with TARP occurrence. The presence of TARP (estimate: -0.042 mm2/month; P = 0.001) and female gender (estimate: -0.035 mm2/month; P = 0.006) were associated with slower rates of RPE dehiscence enlargement over time. Faster rates of visual improvement were observed in eyes with TARP compared with those without TARP (estimate = -0.010 logarithm of the minimum angle of resolution/month if TARP was present; P = 0.008). CONCLUSION: Retinal pigment epithelium tear repair with TARP and female gender were associated with slower RPE degeneration after RPE tears. The presence of TARP was associated better visual prognosis. Additional research on factors promoting TARP development may have therapeutic and prognostic implications.

Case Report: Peripheral Retinal Ischemia and Retinal Neovascularization in von Willebrand Disease.

SIGNIFICANCE: Although von Willebrand disease is the most common inherited bleeding disorder, there are only a few published reports of ocular complications. To our knowledge, this is the first case of peripheral retinal ischemia and retinal neovascularization in a patient with von Willebrand disease. PURPOSE: This study aimed to demonstrate the value of multispecialty care when exploring a diagnosis for bilateral retinopathy. CASE REPORT: A 55-year-old African American woman presented with peripheral retinal hemorrhages on routine examination. She was asymptomatic and did not have any personal or family history of bleeding disorders. Blood work was ordered, and she was referred to a retinal specialist who found peripheral telangiectasia, retinal ischemia, and leakage on fluorescein angiography, consistent with retinal neovascularization. Laser photocoagulation was performed while numerous specialists were consulted to determine the cause for her retinopathy. Laboratory testing confirmed low-grade type 1 von Willebrand disease. She was monitored without systemic treatment. She remained stable and asymptomatic, but her retinal neovascularization did not regress fully, so laser treatment was repeated. CONCLUSIONS: This case described a new finding of peripheral retinal ischemia and retinal neovascularization in von Willebrand disease. It was discovered in an asymptomatic patient who did not have a history of bleeding but presented with bilateral retinal hemorrhages. Diagnosis was challenging because of the high degree of variation in this bleeding disorder, requiring extensive testing and careful consideration of the individual's clinical profile. Most people with von Willebrand disease do not know they have the disease because symptoms are mild or absent, so most cases are unreported. The von Willebrand factor is poorly recognized in ocular disease, but given its role in angiogenesis, it may be a valuable target to consider in future research.

Interferon-γ inhibits retinal neovascularization in a mouse model of ischemic retinopathy.

Interferon-γ (IFNG) is one of the key cytokines that regulates both innate and adaptive immune responses in the body. However, the role of IFNG in the regulation of vascularization, especially in the context of Vascular endothelial growth factor A (VEGFa)-induced angiogenesis is not clarified. Here, we report that IFNG shows potent anti-angiogenic potential against VEGFa-induced angiogenesis. IFNG significantly inhibited proliferation, migration, and tube formation of Human umbilical vein endothelial cells (HUVECs) both under basal and VEGFa-treated conditions. Intriguingly, Knockdown (KD) of STAT1 abolished the inhibitory effect of IFNG on VEGFa-induced angiogenic processes in HUVECs. Furthermore, IFNG exhibited potent anti-angiogenic efficacy in the mouse model of oxygen-induced retinopathy (OIR), an in vivo model for hypoxia-induced retinal neovascularization, without induction of functional side effects. Taken together, these results show that IFNG plays a crucial role in the regulation of VEGFa-dependent angiogenesis, suggesting its potential therapeutic applicability in neovascular diseases.

Early pars plana vitrectomy for proliferative diabetic retinopathy: update and review of current literature.

PURPOSE OF REVIEW: Diabetic retinopathy (DR) is one of the leading causes of preventable vision loss in the world and its prevalence continues to increase worldwide. One of the ultimate and visually impairing complications of DR is proliferative diabetic retinopathy (PDR) and subsequent tractional retinal detachment. Treatment modalities, surgical techniques, and a better understanding of the pathophysiology of DR and PDR continue to change the way we approach the disease. The goal of this review is to provide an update on recent treatment modalities and outcomes of proliferative diabetic retinopathy and its complications including tractional retinal detachment. RECENT FINDINGS: Panretinal photocoagulation (PRP), anti-vascular endothelial growth factor (anti-VEGF), and pars plana vitrectomy are the mainstay of PDR treatment. However, PRP and anti-VEGF are associated with significant treatment burden and multiple subsequent treatments. Early vitrectomy is associated with vision preservation, less treatment burden, and less subsequent treatments than therapy with PRP and anti-VEGF. SUMMARY: Concerning costs, high rates of noncompliance in the diabetic population and significant rates of subsequent treatments with initial PRP and anti-VEGF, early vitrectomy for diabetic retinopathy in patients at risk of PDR is a cost-effective long-term stabilizing treatment for diabetics with advanced disease.

BACILLARY LAYER DETACHMENT BECAUSE OF MACULAR NEOVASCULARIZATION.

PURPOSE: To describe the clinical and multimodal imaging features of bacillary layer detachment (BD), and its response to intravitreal anti-vascular endothelial growth factor therapy, in eyes with macular neovascularization. METHODS: Retrospective, observational case series of 14 eyes (14 patients, 7 men) imaged with eyes (14 patients, 7 men) were imaged with spectral-domain optical coherence tomography, and either fluorescein angiography or optical coherence tomography angiography. Therapeutic response was monitored with serial imaging and best-corrected visual acuity assessments. RESULTS: The mean age was 75 ± 13 (range: 45-96) years, with mean follow-up duration of 27 ± 21 (range: 1-56) months. Neovascular age-related macular degeneration was found in 71% (10/14) eyes. Type 2 macular neovascularization lesions were associated with BD in all 14 eyes. Subretinal hemorrhage was noted in 79% (11/14) eyes. BD promptly resolved after intravitreal antivascular endothelial growth factor therapy in all eyes. The baseline best-corrected visual acuity improved from logarithm of the minimum angle of resolution 0.84 ± 0.32 (Snellen equivalent 20/138) to logarithm of the minimum angle of resolution 0.48 ± 0.31 (Snellen equivalent 20/60) at the last follow-up, with treatment of the macular neovascularization. CONCLUSION: Type 2 macular neovascularization and subretinal hemorrhage are associated with BDs, which may be due to a rapid influx of exudative fluid into the potential space between the external limiting membrane and ellipsoid zone. Intravitreal antivascular endothelial growth factor therapy results in rapid resolution of BDs and visual improvement in most eyes.

MicroRNA-409-5p promotes retinal neovascularization in diabetic retinopathy.

BACKGROUND: Retinal neovascularization, which is characterized by the increased proliferation, migration, and tube formation of retinal microvascular endothelial cells (RMECs), contributes to the progression of diabetic retinopathy (DR). MiR-409-5p has been reported to be upregulated in peripheral blood of DR patients and in vascular endothelial growth factor (VEGF)-induced RMECs. However, the role of miR-409-5p in retinal neovascularization of DR remains unelucidated. METHOD: The expression of miR-409-5p was measured in retinal tissues of streptozocin-induced and db/db diabetic mice, in high glucose-induced mouse RMECs (mRMECs), and in vitreous fluid of proliferative DR patients. Antagomir of miR-409-5p was intravitreally injected into diabetic mice. Proliferation, migration, and tube formation were detected using cell counting kit-8 assay, transwell assay, and microscope observation, respectively. Luciferase reporter assay was used to detect the direct interaction between miR-409-5p and peroxisome proliferator-activated receptor-α (PPARα). RESULT: MiR-409-5p was upregulated in retinal tissues of diabetic mice, in high glucose-induced mRMECs, and in vitreous fluid of proliferative DR patients. The knockdown of miR-409-5p attenuated retinal neovascularization in vivo. The overexpression of miR-409-5p promotes the proliferation, migration, and tube formation, and increased VEGF expression and secretion, while the knockdown of miR-409-5p suppressed the VEGF-induced retinal neovascularization in vitro. PPARα is a downstream target of miR-409-5p, and PPARα overexpression negated the promotion of miR-409-5p overexpression on the proliferation, migration, and tube formation of mRMECs. CONCLUSION: Our findings demonstrated that miR-409-5p acted as a neovasculogenic factor in DR, and anti-miR-409-5p therapy may provide a novel strategy in treating DR.

Neovascular glaucoma in a pediatric patient with neurofibromatosis type 1: a case report.

BACKGROUND: To report a case of a young patient with neurofibromatosis type 1 (NF1). METHODS: Here we review the treatment administered to a 7-year-old NF1 patient with neovascular glaucoma as the primary diagnosis. CASE PRESENTATION: A 7-year-old boy developed visual loss in the right eye associated with periocular pain and ipsilateral headache that had persisted for 1 week. The patient's condition did not improve after treatment with topical or systemic glaucoma medications. Fundus examination of the right eye showed superotemporal retinal vasoproliferative tumors (RVPT). Near-infrared reflectance scans of the left eye's fundus revealed bright patchy regions, scattered across the posterior pole; systemic examination showed café-au-lait spots all over the patient's body. The patient had a clear family history. Genetic testing confirmed NF1. The right eye was treated with intravitreal ranibizumab injection, retinal lesion cryotherapy, and transscleral ciliary body photocoagulation. After treatment, RVPT scarring was observed. The patient's intraocular pressure remained within normal limits. CONCLUSIONS: We report a rare case of neurofibromatosis in a pediatric patient with neovascular glaucoma accompanied by RVPT. We suggest that evaluations of young patients with neovascular glaucoma should include careful attention to the overall condition of the patient and his/her parents, as well as family history. If necessary, NF1 molecular testing should be performed to avoid a missed diagnosis or misdiagnosis.

Nanoscale delivery systems in treatment of posterior ocular neovascularization: strategies and potential applications.

Pathologic posterior neovascularization of eye is a major cause of irreversible vision loss and limitations of therapeutics to be successfully delivered to back of the eye has been a main obstacle for its effective treatment. Current pharmacological treatment using anti-VEGF agents being delivered intravitreally are effective but complicated due to anatomical and physiological barriers, as well as administration of high and frequent doses. With expanding horizons of nanotechnology, it can be possible to formulate promising nanoscale delivery system to improve penetration and sustained the release of therapeutic in posterior segment of the eye. Taking into consideration advances in the field of nanoscale delivery systems, this special report focuses on emerging strategies and their applications for treatment of posterior ocular neovascularization.

Focal retinal pigment epithelium atrophy at the location of type 3 neovascularization lesion: a morphologic feature associated with low reactivation rate and favorable prognosis.

PURPOSE: To investigate the clinical significance of focal retinal pigment epithelium (RPE) atrophy in the eyes with type 3 neovascularization. METHODS: This retrospective study included 184 eyes those were diagnosed with type 3 neovascularization and were treated with antivascular endothelial growth factor (VEGF) therapy. Focal RPE atrophy was defined as a localized RPE atrophy found at the same location as the type 3 lesion. The incidence of reactivation after 3 loading injections and the visual outcomes was compared between a focal RPE atrophy group and a nonfocal RPE atrophy group. In the focal RPE atrophy group, the number of injections was compared between before and after the development of RPE atrophy. RESULTS: The mean follow-up period was 37.6 ± 18.8 months; focal RPE atrophy developed in 24 eyes (13.0%). Reactivation of the lesion after 3 loading injections was significantly less frequent in the focal RPE atrophy group (58.3%) than that in the nonfocal RPE atrophy group (85.0%) (P = 0.004). In the focal RPE atrophy group, the mean best-corrected visual acuity (BCVA) was 0.68 ± 0.28 (Snellen equivalent = 20/95) at diagnosis and 0.70 ± 0.48 (20/100) at the final follow-up. In the nonfocal RPE atrophy group, the values were 0.75 ± 0.34 (20/112) and 1.12 ± 0.68 (20/263), respectively. The BCVA at the final follow-up was significantly better in the focal RPE atrophy group (P < 0.001). The mean number of injections per year was 4.9 ± 1.8 and 1.3 ± 1.6 before and after the development of focal RPE atrophy, respectively (P < 0.001). CONCLUSIONS: Development of focal RPE atrophy was associated with a low incidence of reactivation of type 3 neovascularization and was therefore predictive of a favorable visual prognosis.

Early Recurrent Hemorrhage in Submacular Hemorrhage Secondary to Type 3 Neovascularization or Retinal Angiomatous Proliferation: Incidence and Influence on Visual Prognosis.

PURPOSE: To evaluate the incidence of early recurrent hemorrhage in submacular hemorrhage secondary to type 3 neovascularization or retinal angiomatous proliferation (RAP) and its influence on visual prognosis. METHODS: This retrospective study included 32 eyes with submacular hemorrhage secondary to type 3 neovascularization or RAP that underwent anti-vascular endothelial growth factor (VEGF) therapy. The eyes exhibiting an increase in the extent of hemorrhage within 6 months after hemorrhage development were included in the early recurrent hemorrhage group, and the remaining eyes were included in the non-early recurrent hemorrhage group. The best-corrected visual acuities (BCVAs) measured at the time of hemorrhage development and at 12 months were compared between the two groups. RESULTS: During the follow-up period, 8 eyes underwent vitrectomy to clear vitreous hemorrhage, and the remaining 24 eyes underwent anti-VEGF monotherapy. In the early recurrent hemorrhage group (n = 12), the mean logarithm of the minimal angle of resolution BCVA at the time of hemorrhage development and after 12 months was 1.17 ± 0.40 (Snellen equivalents: 20/295) and 2.35 ± 0.59 (20/4477), respectively. In the non-early recurrent hemorrhage group (n = 20), the corresponding values were 1.07 ± 0.43 (20/234) and 1.44 ± 0.71 (20/550), respectively. The BCVA at 12 months was significantly worse in the early recurrent hemorrhage group (P = 0.003) despite comparable BCVA at diagnosis between the two groups (P = 1.000). CONCLUSIONS: Early recurrent hemorrhage was noted in 37.5% of eyes with submacular hemorrhage secondary to type 3 neovascularization or RAP and was closely associated with a poor prognosis.

Expression of angiopoietin-like protein 8 correlates with VEGF in patients with proliferative diabetic retinopathy.

PURPOSE: To investigate the vitreous and serum levels of angiopoietin-like protein 8 (ANGPTL-8) and vascular endothelial growth factor (VEGF) in patients with proliferative diabetic retinopathy (PDR). The serum levels of these factors were also analyzed in patients with diabetes and no diabetic retinopathy (NDR) and with non-proliferative diabetic retinopathy (NPDR), to detect the possible correlation between the ANGPTL-8 levels and hyperlipidemia. METHODS: Vitreous samples were obtained from 28 patients with PDR and from 12 patients without diabetes and with idiopathic macular hole (IMH). Serum samples were also obtained from 26 patients with NDR and 22 patients with NPDR. ANGPTL-8 levels and other factors were determined using an enzyme-linked immunosorbent assay. RESULTS: The ANGPTL-8 and VEGF levels in the vitreous and serum of the patients with PDR were higher than those in the patients with IMH, and were significantly correlated. The vitreous and serum ANGPTL-8 levels were more correlated with the triglyceride and low-density lipoprotein cholesterol levels than with the high-density lipoprotein cholesterol or total cholesterol levels in the patients with PDR. CONCLUSIONS: The vitreous and serum ANGPTL-8 levels were both upregulated in patients with PDR. There was an association between the elevation in the ANGPTL-8 levels and angiogenic and hyperlipidemic factors in the patients with PDR. These results suggest that ANGPTL-8 is a potential new diagnostic marker and therapeutic target for PDR treatment.

TYPE 1 VERSUS TYPE 3 NEOVASCULARIZATION IN PIGMENT EPITHELIAL DETACHMENTS ASSOCIATED WITH AGE-RELATED MACULAR DEGENERATION AFTER ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY: A Prospective Study.

PURPOSE: To evaluate the response to aflibercept therapy for Type 1 and Type 3 neovascularization in pigment epithelial detachments associated with treatment-naive, neovascular age-related macular degeneration. METHODS: In this multicentered, prospective study, eligible eyes underwent an intravitreal aflibercept injection protocol for 12 months. Visual acuity and morphologic features of the pigment epithelial detachments were compared at baseline and follow-up intervals between eyes with Type 1 versus Type 3 neovascularization. RESULTS: Thirty-six eyes were analyzed. At 12 months, Type 1 lesions showed a 4.5 ± 23 Early Treatment of Diabetic Retinopathy Study letter improvement (P = 0.1665) versus a 14 ± 11 (P = 0.0072) letter improvement with Type 3 lesions. Both Type 1 and 3 eyes showed a significant decrease in pigment epithelial detachment size, subretinal fluid, and subretinal hyperreflective material; however, Type 3 eyes had a greater reduction in pigment epithelial detachment size and subretinal hyperreflective material, as well as a reduction in central retinal thickness. Type 1 eyes required an average of 1.636 (range, 1-4) injections to resolve fluid, which was greater than Type 3 eyes, which required an average of 1.143 (range, 1-2) injections (P = 0.0251). CONCLUSION: Intravitreal aflibercept injections were efficacious for pigment epithelial detachments, but baseline and follow-up anatomical and functional outcomes differed in Type 1 versus Type 3 neovascularization. The better response of Type 3 eyes with fewer injections suggests that differentiation of the neovascularization subtype at the initial diagnosis may allow for a more tailored, optimal therapy.

UK Neovascular Age-Related Macular Degeneration Database. Report 6: time to retreatment after a pause in therapy. Outcomes from 92†976 intravitreal ranibizumab injections.

BACKGROUND/AIMS: To study the time to retreatment in eyes with neovascular age-related macular degeneration (nAMD) that had been treatment-free for intervals of 3 months, 6 months, 9 months and 12 months during the maintenance phase of ranibizumab therapy within the UK National Health Service. METHODS: In this multicentre national nAMD database study, structured data were collected from 14 centres (involving 12 951 eyes receiving 92 976 ranibizumab injections). Patients were treated with three fixed, monthly injections in a loading phase of treatment, followed by a pro re nata retreatment regimen in a maintenance phase. Eyes with a treatment-free interval (TFI) of 3 months, 6 months, 9 months or 12 months in the maintenance phase were identified and the time to retreatment after these TFIs was determined. RESULTS: The time to retreatment for the 20th and 50th centiles was 0.58/2.54 months after a 3-month TFI, 2.07/9.62 months after a 6-month TFI, 3.69/15.84 months after a 9-month TFI and 5.90/22.49 months after a 12-month TFI. Following a TFI of 3 months, 6 months, 9 months and 12 months, 68%, 44%, 31% and 21% of eyes required retreatments after an additional 6 months of follow-up, respectively. Similarly, after 12 months of follow-up, 77%, 56%, 43% and 34% of these eyes required retreatment. CONCLUSIONS: This study provides times to retreatment in eyes with nAMD that have been treatment-free for intervals of 3-12 months and demonstrates the likelihood of repeat therapy within the next year, even after a TFI of 12 months. These outcomes can help plan appropriate follow-up intervals for patients who have been treatment-free for intervals of up to 12 months.

Key drivers of visual acuity gains in neovascular age-related macular degeneration in real life: findings from the AURA study.

BACKGROUND/AIMS: To identify predictive markers for the outcomes of anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration (nAMD). METHODS: AURA was a retrospective, observational, multicentre study that monitored the 2-year outcomes following intravitreal ranibizumab treatment in patients with nAMD. Using stepwise regression analysis, we evaluated the association between visual acuity outcomes, baseline characteristics and resource utilisation in order to determine which variables are significantly linked to outcomes in AURA. We also examined the relationship between visual acuity outcomes and number of injections received. RESULTS: Analyses were performed using data from year 1 (n=1695) and year 2 completers (n=1184). Logistic analysis showed that baseline visual acuity score, age at start of therapy, number of ophthalmoscopies and optical coherence tomography (OCT) (combined) and number of injections (ranibizumab) were significant (p<0.05) prognostic factors for vision maintenance (loss <15 letters) or vision gain (≥15 letters). Patients who received >7 injections (in 1 year) or >14 injections (over 2 years) gained more letters and demonstrated greater vision maintenance (loss of <15 letters) than patients who received fewer injections. There was a significant (p<0.05) association between number of injections and national reimbursement schemes and OCT. CONCLUSIONS: A number of factors that are predictive of treatment outcomes in a real-life setting were identified. Notably, the decline of treatment benefits may be linked to number of injections and a failure to visit clinicians and receive OCT as required. These findings may be helpful in guiding ophthalmologist treatment decisions under limited time and financial constraints. TRIAL REGISTRATION NUMBER: NCT01447043.

Changes in intraocular pressure in study and fellow eyes in the IVAN trial.

PURPOSE: To describe changes in intraocular pressure (IOP) in the 'alternative treatments to Inhibit VEGF in Age-related choroidal Neovascularisation (IVAN)' trial (registered as ISRCTN92166560). DESIGN: Randomised controlled clinical trial with factorial design. PARTICIPANTS: Patients (n=610) with treatment naïve neovascular age-related macular degeneration were enrolled and randomly assigned to receive either ranibizumab or bevacizumab and to two regimens, namely monthly (continuous) or as needed (discontinuous) treatment. METHODS: At monthly visits, IOP was measured preinjection in both eyes, and postinjection in the study eye. OUTCOME MEASURES: The effects of 10 prespecified covariates on preinjection IOP, change in IOP (postinjection minus preinjection) and the difference in preinjection IOP between the two eyes were examined. RESULTS: For every month in trial, there was a statistically significant rise in both the preinjection IOP and the change in IOP postinjection during the time in the trial (estimate 0.02 mm Hg, 95% CI 0.01 to 0.03, p<0.001 and 0.03 mm Hg, 95% CI 0.01 to 0.04, p=0.002, respectively). There was also a small but significant increase during the time in trial in the difference in IOP between the two eyes (estimate 0.01 mm Hg, 95% CI 0.005 to 0.02, p<0.001). There were no differences between bevacizumab and ranibizumab for any of the three outcomes (p=0.93, p=0.22 and p=0.87, respectively). CONCLUSIONS: Anti-vascular endothelial growth factor agents induce increases in IOP of small and uncertain clinical significance. TRIAL REGISTRATION NUMBER: ISRCTN92166560.

Short-term choroidal thickness changes in patients treated with either ranibizumab or aflibercept: a comparative study.

PURPOSE: To compare, in neovascular age-related macular degeneration (AMD) patients, short-term choroidal thickness changes in eyes treated using ranibizumab with those in eyes treated using aflibercept. METHODS: This retrospective, observational study included 240 eyes from 240 patients who had been diagnosed with treatment-naive neovascular AMD and treated using three monthly injections of either ranibizumab (ranibizumab group) or aflibercept (aflibercept group). The choroidal thickness change between the time of diagnosis and 3 months later was compared between the two groups. Eyes were then classified into three disease groups: typical neovascular AMD, polypoidal choroidal vasculopathy (PCV) and retinal angiomatous proliferation (RAP). Within each disease group, choroidal thickness change was again compared between the two treatment groups. RESULTS: In the ranibizumab group (n=155), the mean choroidal thicknesses at diagnosis and at 3 months were 255.3±103.9 µm and 242.9±104.8 µm, respectively. In the aflibercept group (n=85), the values were 277.5±119.1 µm and 254.7±114.5 µm, respectively. The decrease was significantly greater in the aflibercept group (p<0.001). In the PCV group, the decrease was greater in the aflibercept group (p=0.001), whereas the difference was not significant in either the typical neovascular AMD group or the RAP group. CONCLUSIONS: A greater decrease in choroidal thickness was noted in eyes treated with aflibercept than in eyes treated with ranibizumab. This difference was more marked in PCV than in other subtypes of neovascular AMD.

Outcomes of intravitreal anti-VEGF therapy in eyes with both neovascular age-related macular degeneration and diabetic retinopathy.

PURPOSE: To investigate the outcomes of intravitreal antivascular endothelial growth factor (VEGF) therapy in eyes with both neovascular age-related macular degeneration (AMD) and diabetic retinopathy (DR). METHODS: Patients from four high-volume referral centres who presented with neovascular AMD and DR, and received intravitreal anti-VEGF therapy, were included. Data retrieved from medical records and multimodal imaging were analysed. RESULTS: Forty-one eyes of 38 patients (21 male, 17 female; mean age 78±8 years) were enrolled. Median follow-up was 28±19 (12-72) months with a mean of 9.2±7.4 intravitreal anti-VEGF injections per eye were administrated. Best-corrected visual acuity (BCVA) was 0.5±0.3 logMAR; it improved significantly at 1 year (0.3±0.3 logMAR; p=0.02) and returned to baseline values at last follow-up visit (0.6±0.4 logMAR; p=0.26). Mean central macular thickness (CMT) significantly decreased from 408±150 µm to 328±104 µm at 1 year (p=0.021) and to 335±127 µm at last follow-up visit (p=0.032). The baseline severity of DR was graded as mild non-proliferative DR (NPDR) in 21 (51%) eyes, moderate NPDR in 14 (34%), severe NPDR in 4 (10%) and inactive proliferative DR in 2 (5%). At last follow-up visit, one eye graded as moderate NPDR improved to mild, one eye graded as severe NPDR improved to mild and one eye graded as severe NPDR was inactivated due to panretinal photocoagulation. CONCLUSIONS: Outcomes analysis of intravitreal anti-VEGF therapy for eyes with both neovascular AMD and DR showed stabilisation of BCVA and reduction of CMT, along with stable or improved DR stage throughout follow-up.