Inflammatory choroidal neovascularization: an update on diagnosis and management

AIMTo evaluate the optical coherence tomographic characteristics of choroidal neovascularisation (CNV) in age related macular degeneration (AMD) and in idiopathic and inflammatory CNV. The use of this technique in the...

Inflammatory choroidal neovascular membranes are challenging to diagnose and manage. A number of uveitic entities may be complicated by the development of choroidal neovascularization leading to a decrease in central visual acuity. In conditions such as punctate inner choroidopathy, development of choroidal neovascularization is extremely common and must be suspected in all cases. On the other hand, in patients with conditions such as serpiginous choroiditis, and multifocal choroiditis, it may be difficult to differentiate between inflammatory choroiditis lesions and choroidal neovascularization. Multimodal imaging analysis, including the recently introduced technology of optical coherence tomography angiography, greatly aid in the diagnosis and management of inflammatory choroidal neovascularization. Management of these neovascular membranes consists of anti-vascular growth factor agents, with or without concomitant anti-inflammatory and/or corticosteroid therapy.

Inflammation plays a key role in the induction of choroidal neovascularization (CNV). Inflammatory choroidal neovascularization (iCNV) is a severe but uncommon complication of both infectious and non-infectious uveitides. It is hypothesized that its pathogenesis is similar to that of wet age-related macular degeneration (AMD), and involves hypoxia as well as the release of vascular endothelial growth factor, stromal cell-derived factor 1-alpha, and other mediators. Inflammatory CNV develops when inflammation or infection directly involves the retinal pigment epithelium (RPE)-Bruch's membrane complex. Inflammation itself can compromise perfusion, generating a gradient of retinal-choroidal hypoxia that additionally promotes the formation of choroidal neovascularization in the course of uveitis. The development of choroidal neovascularization may be a complication, especially in conditions such as punctate inner choroidopathy, multifocal choroiditis, serpiginous choroiditis, and presumed ocular histoplasmosis syndrome. Although the majority of iCNV cases are well defined and appear as the "classic" type (type 2 lesion) on fluorescein angiography, the diagnosis of iCNV is challenging due to difficulties in differentiating between inflammatory choroiditis lesions and choroidal neovascularization. Modern multimodal imaging, particularly the recently introduced technology of optical coherence tomography (OCT) and OCT angiography (noninvasive and rapid imaging modalities), can reveal additional features that aid the diagnosis of iCNV. However, more studies are needed to establish their role in the diagnosis and evaluation of iCNV activity.

To investigate choroidal thickness changes related to the clinical activity of inflammatory choroidal neovascularization in punctate inner choroidopathy/multifocal choroiditis as compared to myopic choroidal neovascularization. Consecutive inflammatory choroidal neovascularization secondary to punctate inner choroidopathy/multifocal choroiditis, and myopic choroidal neovascularization were retrospectively reviewed. By means of enhanced-depth imaging optical coherence tomography, choroidal thickness was assessed at the same location before choroidal neovascularization development, at choroidal neovascularization onset (baseline), and after treatment. Eleven eyes with inflammatory choroidal neovascularization and 11 eyes with myopic choroidal neovascularization were analyzed. Choroidal thickness beneath inflammatory choroidal neovascularization significantly increased at baseline and decreased after therapy ("Sponge sign"), reaching preclinical values. In particular, mean choroidal thickness under inflammatory choroidal neovascularization was 145 ± 85 µm at the preclinical stage, increased to 210 ± 103 µm at baseline (p = 0.006), and decreased to 136 ± 87 µm after treatment (p = 0.017). Conversely, no significant choroidal thickness changes were disclosed in myopic choroidal neovascularization eyes, under any location. Optical coherence tomography-based choroidal thickness evaluation may represent an additional useful tool to monitor inflammatory choroidal neovascularization activity. Moreover, choroidal thickness under choroidal neovascularizations could be used to discriminate the origin of choroidal neovascular membrane, either inflammatory or myopic, in doubtful cases and guide the therapeutic management.

Objective To highlight the safety and efficacy of Tumor Necrosis Factor inhibitors (anti-TNF) in inflammatory choroidal neovascularization (CNV) in the pediatric population. Design Retrospective case series. Participants Three patients, < 16 years old with uveitic inflammatory CNV. Methods Patients received systemic steroids, methotrexate (MTX), intravitreal (IVT) injections of bevacizumab, and anti-TNF (infliximab or adalimumab) in case of refractory leakage. Results Five eyes of three pediatric patients (mean age 6 years old) presenting with CNV and put on anti-TNF were followed up for a minimum of32 months. Four out of five eyes had improved vision, reduced fluid on clinicalexam and macular spectral-domain optical coherence tomography (SD-OCT), and cessation of leakage on fundus fluorescein angiography (FFA) after introduction of anti-TNF agents. Two patients developed minor psoriasis treated topically. Conclusion Anti-TNF agents showed efficacy and safety in a sustainable leakage control of inflammatory pediatric CNV along with improvement in vision.

Bevacizumab in Inflammatory Eye Disease

Purpose: To describe the optical coherence tomography angiography (OCTA) features of active inflammatory choroidal neovascularization (CNV) and characterize the early responses of anti-vascular endothelial growth factor (VEGF) treatment for inflammatory CNV. Methods: OCT angiography images of inflammatory CNV were acquired and analyzed using the RTVue XR Avanti with AngioVue at baseline as well as fluorescein angiography and spectral-domain optical coherence tomography (SD-OCT). OCTA scans were sequentially obtained 1 day before treatment, 1 day, 7 days, 14 days, and 30 days after anti-VEGF injection. Changes of the selected area and flow area of CNV on OCTA were measured along with those of the central macular thickness (CMT) on corresponding SD-OCT. Results: 19 eyes of 18 uveitic patients (mean age: 36.83 ± 10.05 years) presenting with active CNV were included in the prospective case series. The OCTA showed a 100% sensitivity for inflammatory CNV detection in 23 of 23 CNV lesions, revealing prevailing two neovascular phenotypes: vascular loops and intertwined nets. After anti-VEGF injection, as early as the 1-day follow-up, the mean selected area and the mean flow area of inflammatory CNV on OCTA were significantly reduced (both P < .05) while the average CMT on SD-OCT did not change until the 7-day follow-up. OCTA was able to detect the reincrease of capillary density and vessel size predominantly in the second phenotype 14–30 days after anti-VEGF injection. Conclusions: OCTA not only allows for noninvasive detection of inflammatory CNV with a high sensitivity but also facilitates its sequential observation after anti-VEGF treatment. The treatment outcomes are observable at day 1 post treatment. OCTA may be a useful tool for diagnosing inflammatory CNV and evaluating the early response to anti-VEGF treatment.

Background and Objectives:The aim was to study the clinical profile of inflammatory choroidal neovascularization (CNV) and its treatment response to intravitreal bevacizumab or ranibizumab on pro re nata (PRN) basis in Indian eyes.Materials and Methods:This was a retrospective case series of consecutive patients with inflammatory CNV treated with anti-vascular endothelial growth factor (anti-VEGF) in a tertiary eye care center in Eastern India between 2009 and 2014. The data about clinical features, investigations, treatment, and outcomes were obtained from the medical records. We included patients with active inflammatory CNV but with no evidence of inflammation and were treated with anti-VEGF alone, with a minimum follow-up of 6 months. Main outcome measures were a clinical and etiological profile of inflammatory CNV in Indian eyes and their response to treatment.Results:Thirty eyes of 28 patients were included in the study. The mean follow-up was 17.93 ± 14.28 months (range 6–53 months). In our cohort, seven (23.33%) eyes had inflammatory CNV secondary to idiopathic choroiditis, four (13.33%) eyes had toxoplasmosis, idiopathic panuveitis, and Vogt Koyanaki Harada's disease each. Three (10%) eyes had geographic helicoid peripapillary choroidopathy and tubercular choroiditis each. Remaining two (6.66%) eyes had punctate inner choroidopathy, while multifocal choroiditis with panuveitis, resolved endogenous endophthalmitis and Hansen's diseases were the etiology in one (3.33%) case of inflammatory CNV each. The mean number of injections were 2.76 (range 1–5). Among thirty eyes of inflammatory CNV, 16 (53.3%) eyes showed improvement, eight (26.6%) maintained the same vision, whereas six (20%) eyes showed deterioration of vision.Interpretations and Conclusion:Idiopathic choroiditis was the most common cause of inflammatory CNV and PRN intravitreal anti-VEGF (ranibizumab or bevacizumab) appears to have effective treatment response.

Purpose: To describe demographic features and clinical and imaging characteristics of inflammatory choroidal neovascularization (CNV) in a Chinese population.Methods: A retrospective case review of patients with CNV secondary to uveitis from 2002 to 2013.Results: A total of 125 patients (150 eyes, 166 CNVs; bifocal CNVs in 16 eyes), 64% of whom were women, were reviewed. The mean age was 35.86 years. The proportions of patients with punctate inner choroidopathy (PIC), multifocal choroiditis (MFC), and Vogt-Koyanagi-Harada (VKH) were 50.4, 22.4, and 8%. All of the cases were classic CNV in fluorocein angiography and type 2 CNV in OCT. The proportion of subfoveal lesions in active CNV (30.09%) was less than that in inactive CNV (60.38%).Conclusions: PIC, MFC, and VKH were the three primary specific types of uveitis with inflammatory CNV in this study. Inflammatory CNV tended to break though the retinal pigment epithelium and beneath the neurosensory retina. Moreover, inflammatory CNV was usually nonsubfoveal when it occurred.

ABSTRACTPurpose: To analyze clinical profile and management of inflammatory choroidal neovascularization (CNV) seen at a referral uveitis clinic.Methods: Records of patients with uveitis and inflammatory CNV from January 1989 to April 2012 were retrieved and the data was analyzed.Results: Forty-nine eyes of 43 patients were included. Mean age at presentation was 35.81 years. Eighteen eyes (36.7%) had infective etiology and 31 eyes (63.2%) had non-infective etiology. The most common location of the CNV was subfoveal, in 18 eyes (36.7%). Management included corticosteroids in all patients, additional immunosuppressive in 17 eyes (34.6%) and local management, with anti-VEGF injections in 29 eyes (63%). Visual outcome was favorable in 37 eyes (75%).Conclusion: Inflammatory CNV can be successfully managed and vision can be improved or stabilized, with prompt and adequate therapy of the underlying uveitic disease coupled with additional local therapy to selectively target the CNV.

Inflammatory choroidal neovascularization (iCNV) is a rare complication of uveitis but is a major cause of vision compromise in affected patients. Fluorescein angiography (FA) has been the gold standard for diagnosis. However, it is an invasive modality and when used alone, it might be difficult to distinguish iCNV from inflammatory lesions. Optical coherence tomography (OCT) is a noninvasive and rapid imaging modality that can provide additional features to diagnose iCNV. OCT angiography (OCTA) uses intrinsic motion contrast to visualize flow and is useful to distinguish iCNV from inflammatory lesions. However, its role in evaluating iCNV activity and treatment response is still unclear and more studies are required to reach consensus. In conclusion, the use of data from multimodal imaging is necessary to identify and promptly treat iCNV, thus preserving patient vision.

Objective: Inflammatory choroidal neovascularization (i-CNV) is an infrequent but sight-threatening complication of posterior uveitis. Although it can occur in a wide range of infectious and non-infectious uveitides, presence of simultaneous bilateral i-CNV is rare. In this report, we present a unique case of bilateral simultaneous i-CNV in a young patient of healed tubercular serpiginous-like choroiditis.Method: A 20-year-old male presented with recent worsening of vision in the right eye for one month. Fundus examination revealed bilateral multifocal healed choroiditis lesions with right eye tiny subfoveal hemorrhage raising the suspicion of an underlying choroidal neovascularization. Fundus fluorescein angiography and optical coherence tomography confirmed presence of choroidal neovascular membrane in both eyes.Result:Resolution of activity was noted in both eyes after bilateral sequential intravitreal bevacizumab injections.Conclusion:Inflammatory choroidal neovascularization may be seen in patients with healed tubercular serpiginous-like choroiditis, after a long period of quiescence. Simultaneous bilateral presentation is rare but possible, requiring mandatory multimodal imaging of both eyes under high index of suspicion. Early institution of anti-vascular endothelial growth factor may salvage optimum vision in such a scenario.

To investigate the influence of age, gender, and underlying disease on the optical coherence tomography (OCT) features of choroidal neovascularization (CNV) secondary to inflammation, myopia (mCNV), and age-related macular degeneration (AMD-CNV). Demographic and clinical data of eyes with treatment-naive inflammatory CNV, mCNV, and Type 2 AMD-CNV were collected. Optical coherence tomography images were reviewed to determine the presence of pitchfork sign, pigment epithelial detachment, subretinal fluid (SRF), intraretinal cysts, subretinal hyperreflective material, atrophy, and outer retinal disruption graded 1 to 4. The influence of demographics and underlying etiology on OCT signs was investigated. One hundred and eighty-five eyes from 179 patients were enrolled. The mean [SD] age was 36 [±14.4], 62 [±18], and 77 [±8] for the inflammatory CNV, mCNV, and AMD-CNV, respectively (P < 0.001). Multiple linear regression showed that the presence of pitchfork sign was negatively associated with age (P < 0.0001), regardless of underlying disease. By contrast, the SRF, pigment epithelial detachment, intraretinal cysts, and the outer retinal disruption were all positively influenced by age, regardless of gender and underlying disease (all P < 0.01). Logistic regression showed that none of the OCT signs increased the likelihood for diagnosis of inflammatory CNV. By contrast, the absence of SRF was suggestive for mCNVs, and the presence of pigment epithelial detachment and SRF was suggestive for AMD-CNVs. The age of the patient had a significant effect on the OCT appearance of the CNV, particularly the presence of a pitchfork sign, regardless of the underlying etiology. The absence of SRF was suggestive for a diagnosis of mCNVs. The presence of SRF and pigment epithelial detachment was suggestive for AMD-CNVs.

To assess the effects of intravitreal bevacizumab injection as primary treatment of inflammatory choroidal neovascularization (CNV). Data for nine consecutive patients with newly diagnosed inflammatory CNV who were treated with intravitreal bevacizumab (1.25 mg) injection were reviewed retrospectively. Main outcome measures were best-corrected visual acuity, foveal thickness measured by optical coherence tomography (OCT), and complete resolution of CNV. CNV resolved completely in 9 (100%) of 9 affected eyes. At the last examination, visual acuity was improved in 8 eyes (88.8%), stable in 1 (11.2%), and worse in 0. Over a mean follow-up of 7.1 months (range, 6-10 months), 7 eyes received 1 injection, 1 eye developed CNV recurrence and required a second injection, and 1 eye required a third injection. Foveal thickness by OCT decreased significantly (P = 0.049) after treatment. In this small case series of eyes with limited follow-up, intravitreal bevacizumab injection for treatment of inflammatory CNV was found to be safe and was associated with favorable visual outcomes for both subfoveal and juxtafoveal or extrafoveal inflammatory CNV.

Aim: To report the visual and angiographic outcomes after combination photodynamic therapy (PDT) and immunosuppression for inflammatory subfoveal choroidal neovascularisation (CNV). Methods: Retrospective review of six consecutive patients, five female...