Birdshot Chorioretinopathy Research Articles

An update of multimodal imaging in white dot syndrome

Abstract: The white dot syndromes are a group of phenotypically similar disorders characterized by multiple lesions at the level of the outer retina, retinal pigment epithelium, and choroid. Common white dot syndromes whose imaging modalities have been described in this article are multiple evanescent white dot syndrome, acute posterior multifocal placoid pigment epitheliopathy, acute zonal occult outer retinopathy, multifocal choroiditis and panuveitis, punctate inner choroidopathy, serpiginous choroiditis, and birdshot chorioretinopathy. The various imaging modalities help us to better understand the pathophysiology of the various entities and help in diagnosing, monitoring, and prognosticating them. Optical coherence tomography angiography (OCTA) is a comparatively newer tool that helps us to visualize lesions in the choroid that correlate with indocyanine green angiography (ICGA) findings. Even though it is of limited value and cannot replace ICGA, it had gained considerable interest among ophthalmologists. Similarly, the noninvasive nature of modalities such as fundus autofluorescence and OCT makes them appealing and preferable over invasive techniques such as fundus fluorescein angiography and ICGA.

Single-cell profiling identifies a CD8bright CD244bright Natural Killer cell subset that reflects disease activity in HLA-A29-positive birdshot chorioretinopathy

Birdshot chorioretinopathy is an inflammatory eye condition strongly associated with MHC-I allele HLA-A29. The striking association with MHC-I suggests involvement of T cells, whereas natural killer (NK) cell involvement remains largely unstudied. Here we show that HLA-A29-positive birdshot chorioretinopathy patients have a skewed NK cell pool containing expanded CD16 positive NK cells which produce more proinflammatory cytokines. These NK cells contain populations that express CD8A which is involved in MHC-I recognition on target cells, display gene signatures indicative of high cytotoxic activity (GZMB, PRF1 and ISG15), and signaling through NK cell receptor CD244 (SH2D1B). Long-term monitoring of a cohort of birdshot chorioretinopathy patients with active disease identifies a population of CD8bright CD244bright NK cells, which rapidly declines to normal levels upon clinical remission following successful treatment. Collectively, these studies implicate CD8bright CD244bright NK cells in birdshot chorioretinopathy.

Assessment of Blood Flow Velocity in Retinal Vasculitis Using the Retinal Function Imager-A Pilot Study.

Background: This pilot study aimed to evaluate the Retinal Function Imager (RFI) for visualizing retinal vasculature and assessment of blood flow characteristics in patients with retinal vasculitis. The RFI is a non-invasive imaging device measuring the blood flow velocity (BFV) in secondary and tertiary retinal vessels using hemoglobin as an intrinsic motion-contrast agent. Methods: To test the feasibility of the RFI for patients with retinal vasculitis, capillary perfusion maps (nCPMs) were generated from 15 eyes of eight patients (five females; mean age: 49 ± 12 years) with a mean uveitis duration of 74 ± 85 months. Five of these patients had birdshot chorioretinopathy, and three had primarily non-occlusive venous retinal vasculitis of unknown origin. To reflect that the BFV may be more reduced in patients with prolonged disease, patients were classified into a short-term (uveitis duration: 8-15 months) and a long-term uveitis group (uveitis duration: 60-264 months). Data were compared with healthy controls (16 eyes of 11 patients; mean age 45 ± 12 years; 8 females). Results: The mean BFV in the controls was 3.79 ± 0.50 mm/s in the retinal arteries and 2.35 ± 0.44 mm/s in the retinal veins, which was significantly higher compared to the retinal vasculitis group. Patients revealed an arterial BFV of 2.75 ± 0.74 mm/s (p < 0.001) and a venous BFV of 1.75 ± 0.51 mm/s (p = 0.016). In the short-term group, a trend towards a decreased venular and arteriolar BFV was seen, while a significant reduction was observed in the long-term group. The patients' microvasculature anatomy revealed by the nCPMs appeared unevenly distributed and a lower number of blood vessels were seen, along with a lower degree of complexity of their branching patterns, when compared with controls. Conclusions: This study demonstrated a reduction in venular and arteriolar BFVs in patients with retinal vasculitis. BFV alterations were already observed in early disease stages and became more pronounced in progressed disease. Additionally, we showed that retinal microvasculature changes may be observed by nCPMs. Retinal imaging with the RFI may serve as a diagnostic and quantifying tool in retinal vasculitis.

Fractal Changes of the Retinal Microvasculature in Birdshot Chorioretinopathy.

Retinal vascular disorders are associated with lower fractal dimension (FD). We analyzed FD in birdshot chorioretinopathy (BSCR). This was a retrospective cohort study. We performed optical coherence tomography angiography (OCTA) and analyzed FD of the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CC) using ImageJ. For each vascular layer, we analyzed the presence of BSCR, subjects' age, sex, and presence of diabetes mellitus to determine which may predict lower FD. We compared 28 eyes (14 patients) with BSCR to 34 control eyes (17 patients). Mean FD of BSCR was lower in SCP (1.584 [± 0.126] vs 1.706 [± 0.118], P < 0.001), DCP (1.637 [± 0.134] vs 1.780 [± 0.096], P < 0.001), and CC (1.884 [± 0.063] vs 1.917 [± 0.047], P = 0.036). FD of SCP was lower per increasing year (0.005 [P = 0.014]). Male patients had lower FD-DCP (0.101 [P = 0.043]). In BSCR, fractal analysis showed significant involvement of the SCP, DCP, and to a lesser extent the CC. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Application of Ophthalmic Electrophysiology in Inflammatory Disorders of Retina and Optic Nerve.

This review covers the utility of electrophysiological studies relevant to inflammatory diseases of the retina in conditions such as acute posterior multifocal placoid pigment epitheliopathy, acute zonal occult outer retinopathy, Adamantiades-Behçet disease, autoimmune retinopathy and neuro-retinopathy, birdshot chorioretinopathy, multiple evanescent white dot syndrome, and Vogt-Koyanagi-Harada disease. Electrophysiological studies can help with the diagnosis, prognostication, evaluation of treatment effects, and follow-up for these conditions.

Characterization of Retinal Microvascular Abnormalities in Birdshot Chorioretinopathy Using OCT Angiography

To characterize changes in the retinal microvasculature in eyes with birdshot chorioretinopathy (BCR) using OCT angiography (OCTA). Retrospective, observational, single center. Twenty-eight patients (53 eyes) with BCR and 59 age-matched controls (110 eyes). En face OCTA images of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) of each eye were assessed for the presence of microvascular abnormalities and used to measure the vessel and foveal avascular zone (FAZ) areas. A longitudinal analysis was performed with a representative cohort of 23 BCR eyes (16 patients) at baseline and at a 2-year time point. Whole-image vessel density (VD, %), extrafoveal avascular zone (extra-FAZ) VD (%), and FAZ area (%) were calculated and compared between control and BCR eyes. The frequency of microvascular abnormalities in BCR eyes was recorded. In the SCP, increased intercapillary space and capillary loops were common features present on OCTA images. Whole-image and extra-FAZ VD were lower in the BCR group compared with controls (P < 0.0001 [SCP and DCP]). Foveal avascular zone area was enlarged in BCR eyes (P= 0.0008 [DCP]). Worsening best-corrected visual acuity was associated with a decrease in whole-image and extra-FAZ VD in the SCP (P<0.0001 for both) and the DCP (P < 0.005 for both). Multivariable analysis, with vessel analysis parameters as outcomes, demonstrated that increasing age, increasing disease duration, lower central subfield thickness, and treatment-naive eyes (compared with those on only biologics) were associated with a significant decrease in both DCP whole-image and extra-FAZ VD. Increasing disease duration was associated with a significant decrease in both SCP whole-image and extra-FAZ VD. Longitudinal analysis demonstrated no significant difference in any vessel analysis parameters except for an increase in DCP FAZ area. Our results demonstrate a significant a decrease in VD in BCR eyes and an association on multivariable analysis with disease duration. Quantifying VD in the retinal microvasculature may be a useful biomarker for monitoring disease severity and progression in patients with BCR. Further studies with extended longitudinal follow-up are needed to characterize its utility in monitoring disease progression and treatment response. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Indolent nonprogressive multifocal choroidal lymphoid lesions with late development of systemic lymphoma

Purpose: To report a case of indolent nonprogressive multifocal choroidal lymphoid lesions with late development of pulmonary low-grade B-cell lymphoma after lymphoid lesion regression. Methods: Case report. Results: A 79-year-old male was followed with ocular and systemic surveillance over a sixteen-year period for unilateral nonprogressive choroidal lesions presumed to be a benign lymphocytic disease of the choroid. Workups for systemic lymphoma and birdshot chorioretinopathy were negative. After sixteen years of observation, the choroidal lesions had largely regressed. Recent diagnosis of atrial fibrillation led to an incidental discovery of a right lower lobe lung lesion measuring 4.5 cm. Computerized tomography-guided biopsy showed low-grade B-cell lymphoma. There was no additional systemic disease detected. The patient underwent right lower lobectomy revealing extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. Conclusion: Patients with indolent nonprogressive multifocal choroidal lymphoid lesions should be monitored regularly for late systemic disease, which although rare, can develop even after years of follow-up.

Znaczenie elektrofizjologii siatkówki w chorioretinopatii typu Birdshot

Birdshot chorioretinopathy is a rare disease of probable autoimmune origin. Periodic retinal electrophysiological testing plays a significant role in the diagnosis and monitoring of this disease. This article reviews the literature available in pubmed from1988–2022 on Birdshot chorioretinopathy, with a focus on retinal electrophysiological studies.

Indocyanine Green Angiography of Optic Disc Granuloma in Ocular Sarcoidosis.

To report novel indocyanine green angiography (ICG) findings of optic disc granulomas secondary to sarcoidosis. Observational case report. A 36-year-old white male, who had previously been evaluated for birdshot chorioretinopathy and tested HLA-A29 negative, was referred for evaluation of choroidal lesions in both eyes. Fundus examination revealed ovoid choroidal lesions bilaterally in the posterior pole. Optical coherence tomography demonstrated bilateral focal choroidal elevations in the posterior pole and optic discs consistent with granulomas. ICG revealed diffuse choroidal hypocyanescent spots with late-phase focal hypercyanescence of the optic discs in both eyes corresponding to the granulomas. After three months of prednisone and immunomodulatory treatment, the granulomas improved and the optic disc hypercyanescence resolved. We describe a case of ocular sarcoidosis mimicking birdshot-like lesions, and ICG findings revealed late hypercyanescence, which resolved with treatment.

Retraction of cystoid macular edema from the fovea after intravitreal anti-VEGF therapy for birdshot chorioretinopathy.

To report the effect of anti-vascular endothelial growth factor inhibitor (anti-VEGF) on fovea-involving cystoid macular edema in a patient with Birdshot chorioretinopathy. A 42-year-old male patient presented to our hospital with bilateral posterior uveitis with retinal vasculitis, cystoid macular edema and optic disc edem a. He was diagnosed with birdshot chorioretinopathy based on clinical appearance and tissue type HLA-A29. The patient underwent vitrectomy in the right eye without any change in visual acuity. Retinal leakage was reduced by oral prednisolone, which could not be tapered below 50 mg per day without relapse. Oral prednisolone, topical dexamethasone and subtenonal kenalog were associated with intraocular pressure rise in both eyes. Hence, his uveitis responded to steroids, but there was no detectable effect of any steroid-sparing immunomodulatory drugs. The patient had been on oral prednisolone 50 mg for five years when it was decided to attempt intravitreal VEGF inhibitor injection therapy. The anti-VEGF therapy diminished cystoid macular edema in the fovea and improved the visual acuity. Here we report for the first time the long-term outcomes of anti-VEGF injections on fovea-involving cystoid macular edema in Birdshot chorioretinopathy to keep steroid at the minimal possible doses and preserve a satisfying visual acuity level.

Optical coherence tomography angiography in birdshot chorioretinopathy.

To describe the retinal vascular changes in birdshot chorioretinopathy (BSCR) using optical coherence tomography angiography (OCTA) and to compare them with changes in macular thickness. In this multicenter study, patients with a diagnosis of BSCR and a positive HLA-A29 underwent fluorescein angiography, spectral domain optical coherence tomography (SD-OCT), and OCTA. The foveal avascular zone (FAZ) and the area of capillary non-perfusion were manually measured by two examiners in fluorescein angiography (FA) and 3 × 3-mm OCTA images of the superficial retinal layer. These measurements were compared to central retinal thickness. To calculate normal capillary density, we collected data from 22 controls who had OCTA performed on one visit only. A total of 44 eyes with BSCR were enrolled. The mean automated parafoveal superficial capillary density in BSCR eyes was 0.47 ± 0.03. The differences between the foveal capillary density of BSCR patients and healthy subjects were statistically significant (P < 0.001). The mean area of FAZ manually measured on the 3 × 3 mm unsegmented OCTA images was larger in eyes with BSCR (1.34 ± 0.41 mm2; P < 0.0001). Measurement of FAZ area showed good interobserver (κ 0.88) and intraobserver repeatability (κ 0.79) on OCTA images. The intraclass correlation coefficient for FAZ measurements on FA between the two observers was 0.48. The OCT retinal thickness maps of all BSCR eyes demonstrated statistically significant thinning compared to those of control subjects (P < 0.01). Our study demonstrates the potential contribution of OCTA as a new non-invasive imaging technology that monitors disease activity in BSCR patients.

Long-Term Outcomes of Birdshot Chorioretinopathy Treated with Corticosteroids: A Case Reports.

To report the progression of patients diagnosed with birdshot chorioretinopathy (BSCR) initially treated with corticosteroids. We included 39 BSCR patients that were followed for ≥1 year. We analyzed their progression under treatment after 1, 3, 6 months, 1 year, and at the end of follow-up. In order to determine the efficiency of initial loading doses, patients were classified into two groups according to their initial treatment: methylprednisolone followed by prednisone (n = 28) and prednisone alone (n = 11). At the end of follow-up, 31/39 (79.5%) patients had reached inflammation control. Thirteen out of 28 (46.4%) and 6/11 (54.5%) patients were treated exclusively with corticosteroids, and 18/19 (94.7%) of them had reached inflammation control at the end of follow-up; their mean (range) corticosteroid dose was 3.5 (0-10) mg/day. We found that the prolonged corticosteroid therapy treatment strategy resulted in inflammation control in half of BSCR patients. This control was maintained with low doses of cortisone, usually <5 mg/day.

Birdshot chorioretinopathy in a South Asian patient

To describe the clinical features of a South Asian patient with HLA-A29-positive birdshot chorioretinopathy (BSCR). A 54-year-old South Asian woman presented with blurred vision and floaters. The ophthalmic examination showed bilateral vitritis and retinal vasculitis. Fluorescein angiography revealed a bilateral disc and retinovascular leakage along the arcades. On indocyanine green angiography, multiple hypo-fluorescent lesions were found. Work-up revealed positive HLA-A29. BSCR is primarily seen in patients of European descent, but it can occur in other ancestries. We present an HLA-A29-positive BSCR South Asian patient to highlight that this disease can be seen in patients of South Asian descent.

Reactive lymphoid hyperplasia of the uvea in a patient with birdshot chorioretinopathy

An HLA-A29-positive 82-year-old female diagnosed with birdshot chorioretinopathy 15 years earlier presented with recurrent floaters and blurred vision in the right eye. In addition to increased vitreous haze, fundus examination showed multifocal yellow–orange choroidal lesions. These infiltrates corresponded to focal areas of hyporeflective choroidal thickening with optical coherence tomography (Fig. A) consistent with birdshot-related inflammatory infiltrates versus benign reactive lymphoid hyperplasia. Treatment with oral prednisone led to symptomatic improvement and anatomic resolution of the choroidal infiltrate within 4 weeks (Fig. B).

HISTOPATHOLOGIC CONFIRMATION OF LYMPHOCYTIC INFILTRATION OF THE OPTIC NERVE AND INNER RETINA IN BIRDSHOT CHORIORETINOPATHY.

To describe new histological findings involving the inner retina in birdshot chorioretinopathy. Evaluation of the inner retinal pathology of the eye of a patient with bilateral birdshot chorioretinopathy who underwent enucleation for a unilateral ciliochoroidal melanoma. Histopathological sections showed focal perivascular lymphocytic infiltration at the optic nerve head that extended into the adjacent inner retina, mainly involving the ganglion and nerve fiber layers. We have previously shown that birdshot chorioretinopathy has multiple foci of lymphocytes in the choroid. This is the first report that demonstrates lymphocytic infiltration of the inner retinal layers. This may lead to the bipolar and Müller cell dysfunction that ultimately results in an electronegative electroretinogram.

Birdshot Chorioretinopathy: Report of A Case

Birdshot chorioretinopathy is a rare idiopathic pathology. It is characterized by diffuse white spots in the retina and especially in the middle periphery. All patients are carriers of antigen HLA 29. Its treatment is based in the administration of corticosteroids and suppressant medication. We report the case of a young patient who had birdshot chorioretinopathy.

High Positive Predictive Value of Fluorescein Angiography Contiguous, Perineural Retinal Vascular Leakage Pattern for Birdshot Chorioretinopathy

ABSTRACT Purpose To determine the sensitivity and positive predictive value (PPV) of a contiguous, perineural retinal vascular leakage fluorescein angiography (FA) pattern in birdshot chorioretinopathy (BSCR) patients. Methods Patients with BSCR and other posterior uveitis/retinal vasculitis and a FA were identified. Two graders reviewed the first FA for leakage primarily around the optic nerve and along the larger arcade vessels. We compared the rates of this pattern in BSCR and non-BSCR patients and calculated sensitivity and PPV. We compared clinical characteristics of BSCR patients with and without this pattern. Results 64 BSCR and 98 non-BSCR patients were identified. The FA pattern’s sensitivity, specificity, and PPV were 57.8%, 91.8%, and 82.2%. This pattern was significantly more common in BSCR patients earlier in their disease (p = .004). Conclusions A contiguous, perineural retinal vascular leakage FA pattern can help identify potential BSCR patients for further testing. This pattern is more common closer to symptom onset.

Spectrally resolved autofluorescence imaging in posterior uveitis

Clinical discrimination of posterior uveitis entities remains a challenge. This exploratory, cross-sectional study investigated the green (GEFC) and red emission fluorescent components (REFC) of retinal and choroidal lesions in posterior uveitis to facilitate discrimination of the different entities. Eyes were imaged by color fundus photography, spectrally resolved fundus autofluorescence (Color-FAF) and optical coherence tomography. Retinal/choroidal lesions’ intensities of GEFC (500–560 nm) and REFC (560–700 nm) were determined, and intensity-normalized Color-FAF images were compared for birdshot chorioretinopathy, ocular sarcoidosis, acute posterior multifocal placoid pigment epitheliopathy (APMPPE), and punctate inner choroidopathy (PIC). Multivariable regression analyses were performed to reveal possible confounders. 76 eyes of 45 patients were included with a total of 845 lesions. Mean GEFC/REFC ratios were 0.82 ± 0.10, 0.92 ± 0.11, 0.86 ± 0.10, and 1.09 ± 0.19 for birdshot chorioretinopathy, sarcoidosis, APMPPE, and PIC lesions, respectively, and were significantly different in repeated measures ANOVA (p < 0.0001). Non-pigmented retinal/choroidal lesions, macular neovascularizations, and fundus areas of choroidal thinning featured predominantly GEFC, and pigmented retinal lesions predominantly REFC. Color-FAF imaging revealed involvement of both, short- and long-wavelength emission fluorophores in posterior uveitis. The GEFC/REFC ratio of retinal and choroidal lesions was significantly different between distinct subgroups. Hence, this novel imaging biomarker could aid diagnosis and differentiation of posterior uveitis entities.

Ocular Inflammation Induced by Immune Checkpoint Inhibitors.

Ocular immunotherapy-related adverse events (IRAEs), although rare, can be sight-threatening. Our objective was to analyze ocular IRAEs diagnosed in France from the marketing of immune checkpoint inhibitors (ICPIs) until June 2021 and to review the literature. We collected the cases of 28 patients (36 ocular IRAEs), occurring after an average of 17 weeks (±19). Forty-six percent of patients were treated for metastatic melanoma. Anti-PD1 agents were responsible for 57% of the IRAEs. Anterior uveitis was the most common (44%), followed by panuveitis (28%). Of 25 uveitis cases, 80% were bilateral and 60% were granulomatous. We found one case with complete Vogt-Koyanagi–Harada syndrome and one case of birdshot retinochoroidopathy. The other IRAEs were eight ocular surface disorders, one optic neuropathy, and one inflammatory orbitopathy. Seventy percent of the IRAEs were grade 3 according to the common terminology of AEs. ICPIs were discontinued in 60% of patients and 50% received local corticosteroids alone. The literature review included 230 uveitis cases, of which 7% were granulomatous. The distributions of ICPIs, cancer, and type of uveitis were similar to our cohort. Ocular IRAEs appeared to be easily controlled by local or systemic corticosteroids and did not require routine discontinuation of ICPIs. Further work is still warranted to define the optimal management of ocular IRAEs.

Birdshot Chorioretinopathy: A Review.

Birdshot chorioretinopathy (BSCR) is a bilateral chronic inflammation of the eye with no extraocular manifestations. BSCR affects middle-aged individuals from European descent and is strongly associated with the human leucocyte antigen (HLA)-A29 allele. The immune mechanisms involved are not fully understood, but recent advances have shown the role of Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) in disease pathogenesis. Multimodal imaging, including fluorescein angiography, indocyanine angiography, fundus autofluorescence, and optical coherence tomography, are useful in confirming the diagnosis and monitoring disease activity. Visual field testing is also important to assess the disease progression. To date, there is no consensus for optimal treatment regimen and duration. Local and systemic corticosteroids can be used for short periods, but immunosuppressive or biological therapies are usually needed for the long-term management of the disease. Here, we will review publications focused on birdshot chorioretinopathy to give an update on the pathophysiology, the multimodal imaging, and the treatment of the disease.