Intensity-Modulated Radiation Therapy for Bilateral Choroidal Metastases Involving Macula and Optic Disc.

This case report discusses the case of a 76-year-old woman with choroidal metastasis from breast cancer who was treated with intensity-modulated radiation therapy (IMRT). Choroidal metastasis is a common ocular tumor, and the occurrence of this condition has increased due to improved diagnostic tools and longer survival of metastatic patients. IMRT is an innovative radiation therapy technique that reduces complications and improves the curative effect by concentrating radiation on the tumor while minimizing exposure to surrounding tissues. In this case, the patient had a history of breast cancer and was undergoing chemotherapy when she presented with vision loss and blurred vision. Imaging tests confirmed choroidal metastasis, and IMRT was performed under the guidance of a radiation oncologist. After treatment, the choroidal lesion dramatically reduced in size, and the patient's vision improved. The text concludes that radiation therapy, including IMRT, is becoming more common as a treatment for ocular metastasis to improve vision and preserve the eye. When choosing radiation therapy, it is essential to consider the size of the tumor and the impact on surrounding tissues. IMRT is an effective treatment that enables precise and concentrated irradiation of the tumor tissue while minimizing exposure to normal tissues.

Fungal dysbiosis and decreased tear mucin at the conjunctiva in patients with conjunctival mucosa-associated lymphoid tissue lymphoma.

OBJECTIVE: This study aimed to examine the differences in the fungal microbiome between patients with conjunctival mucosa-associated lymphoid tissue (MALT) and healthy controls using metagenomic analysis. METHODS AND ANALYSIS: This case-control study was conducted at Osaka University Hospital in Osaka, Japan, from April 2015 to March 2022. Twenty-five consecutive patients with conjunctival MALT lymphoma and 25 healthy volunteers were included. Metagenomic analysis using Internal Transcribed Spacer (ITS)1 deep sequencing and hierarchical clustering was performed to investigate differences in the fungal microbiome. To assess tear environmental change, we measured tear mucin concentrations using ELISA. RESULTS: Detailed analyses showed fungal dysbiosis and changes in ß-diversity within the conjunctiva of patients with conjunctival MALT lymphoma. Hierarchical clustering revealed that the participants could be divided into three clusters according to the Malassezia abundance: cluster I (Malassezia abundance above 70%), cluster II (Malassezia abundance 25%-70%) and cluster II (Malassezia abundance below 25%). Most patients were included in cluster I, whereas most of healthy controls were included in cluster III. The differences were significant. Tear mucin concentrations were significantly lower in patients with MALT compared with healthy controls. CONCLUSION: The metagenomic analysis using ITS1 deep sequencing was useful for identifying the differences in commensal fungi between patients with MALT lymphoma and healthy individuals. The increased prevalence of the Malassezia genus and the decreased levels of tear mucin can lead to an allergic response of the conjunctiva, resulting in the pathogenesis associated with conjunctival MALT lymphoma. Therefore, it may be beneficial to initiate treatment when a high abundance Malassezia is detected.

Long-term course with iris changes after trabeculectomy for uveitic glaucoma associated with iris mammillation: a case report.

BACKGROUND: Iris mammillation is a rare disease characterized by the distribution of multiple nodules on the iris surface. The course of uveitic glaucoma with iris mammillation has never been reported. CASE PRESENTATION: A 56-year-old woman, who presented with unilateral decreased vision, visited our hospital for treatment of uveitic glaucoma in the right eye. Multiple nodules were scattered over the iris surface in that eye. This case was diagnosed as iris mammillation on clinical findings. After excluding malignant tumors such as melanoma, trabeculectomy was performed. The resected iris had no pathologically malignant findings. The iris nodules evolved to a sand-like appearance, and the intraocular pressure remained stable without recurrent inflammation 7 years after trabeculectomy. CONCLUSIONS: In a case of unilateral uveitic glaucoma with iris mammillation, filtration surgery was performed after excluding the presence of a malignancy, and the long-term postoperative course has been stable.

Idiopathic Multicentric Castleman Disease Presenting With Hypertensive Choroidopathy: A Case Report.

Castleman disease (CD) is a lymphoproliferative disorder and rarely affects ocular tissue. This study aimed to report a case of hypertensive choroidopathy in a patient with Castleman's disease associated with malignant hypertension. A 39-year-old man visited his local physician with fever, systemic edema, and multiple lymphadenopathies. An inguinal lymph node biopsy indicated CD. One month after the biopsy, the patient noted a blurring of vision. At the time of the initial examination at our hospital, his best-corrected visual acuity (BCVA) was 20/20 in both eyes but there were bilateral multiple Elschnig spots and sprinter hemorrhage at the fundus. Swept-source optical coherence tomography showed intra-retinal fluid, and serous retinal detachment (SRD). Fluorescein angiography revealed multiple punctate hyper fluorescences and indocyanine green angiography showed choroidopathy with increased vascular permeability. A general examination revealed symptoms of cardiac failure and multiple lymphadenopathies. Malignant hypertension with acute glomerulonephritis was diagnosed after a renal biopsy. After antihypertensive treatment, his blood pressure (BP) improved, and the SRD and choroidopathy promptly resolved. Presently, the patient is being followed up without complications. We report a case of hypertensive choroidopathy in a patient with CD associated with malignant hypertension. As a severe elevation in BP can damage choroidal vasculature and lead to vision loss, careful observation and active treatment are necessary.

Barium-induced toxic anterior segment syndrome.

Toxic anterior segment syndrome (TASS) is a rapid-onset inflammation of the eye following uneventful ocular surgery. We report a case of TASS following Baerveldt glaucoma implant (BGI) surgery. Inductively coupled plasma-mass spectrometry (ICP-MS) identified barium in the eye and in the eluate from the bleb of the BGI. We attribute TASS in our patient to the dissolution of barium from the BGI and its entry into the eye, where it causes severe inflammation.

The Efficacy of Golimumab Against Non-Infectious Uveitis: A PRISMA-Compliant Systematic Review and Meta-Analysis.

PURPOSE: In this PRISMA-compliant systematic review and meta-analysis, we aimed to assess the efficacy of golimumab (GOL) against non-infectious uveitis (NIU). METHODS: We included eight articles in the meta-analysis. The primary outcome was inflammation remission. Secondary outcomes were changes in the number of uveitis relapses/attacks, mean best-corrected visual acuity, central macular thickness, and systemic corticosteroid-sparing effects. RESULTS: In total, eight case series with 172 patients (43.6% female) were collected. Patients had 75% (95% CI: 56-87%) of remission; 42% (0.12-0.80) of patients showed improved visual acuity. The average central macular thickness decline was 38 µm (-56.51-18.54). The pooled results showed a significant decrease in the use of systemic corticosteroids. CONCLUSION: This study was limited by the use of non-RCT designs, limited sample sizes for outcomes, and heterogenetic underlying diseases. Our results suggest that GOL is effective against NIU. However, further evidence and analyses are required. (Funding: None; PROSPERO registration: CRD42021266214.).

Factors associated with low prevalence of Fuchs' uveitis syndrome in Japan.

Aim: To investigate the causes of low prevalence of Fuchs' uveitis syndrome (FUS) in Japan. Methods: Medical records of 160 patients diagnosed with FUS at 14 uveitis specialty facilities in Japan were reviewed retrospectively. Results: In 160 FUS patients, mean follow-up period before referral to our uveitis facilities was 31.6 ± 50.9 months. The most common reason for referral was idiopathic uveitis (61.9%), followed by cataract (25.0%), high intraocular pressure (IOP) including glaucoma (16.3%), and FUS (14.4%). Unilateral involvement was 96.9%. The most frequent ocular finding of FUS was anterior inflammation (91.9%), followed by stellate-shaped keratic precipitates (88.1%), cataract/pseudophakia (88.1%), diffuse iris atrophy (84.4%), vitreous opacity (62.5%), heterochromia (53.1%) and high IOP including glaucoma (36.3%). As treatments of these ocular findings, cataract surgery was performed in 52.5%, glaucoma surgery in 10.6%, and vitrectomy in 13.8%. Mean logMAR VA was 0.28 ± 0.59 at the initial visit, and decreased significantly to 0.04 ± 0.32 at the last visit. Proportions of FUS patients with BCVA <0.1 and 0.1 to <0.5 decreased, while that of ≥0.5 increased at the last visit compared with the initial visit. Conclusions: Ocular findings of FUS in Japanese FUS patients were consistent with the characteristic features. The low prevalence of FUS in Japan may be a result of being overlooked and misdiagnosed as mild idiopathic uveitis, cataract, and/or glaucoma.

Clinical Findings of Specular Microscopy Images in Cytomegalovirus Corneal Endotheliitis.

PURPOSE: The aim of this study is to evaluate the usefulness of specular microscopy as an alternative diagnostic tool for cytomegalovirus (CMV) corneal endotheliitis. DESIGN: A retrospective study. METHODS: One hundred and four patients with clinical manifestations of infectious corneal endotheliitis, iridocyclitis, and retinitis were included in this study. The presence of CMV deoxyribonucleic acid (DNA) was confirmed by multiplex polymerase chain reaction (PCR). Viral load was measured using real-time PCR. Corneal endothelium was observed by specular microscopy. The medical records and clinical manifestations of the patients were retrospectively reviewed and linked with the PCR results. RESULTS: Seventeen of 104 cases were CMV endotheliitis and/or iridocyclitis and had no history of intraocular surgery or corneal transplantation. There was a negative correlation between viral load and corneal endothelial cell counts. In 14 of 17 cases, owl's eye cells were observed by specular microscopy. The corneal endothelial cell counts were significantly reduced in the cases in which owl's eye cells were observed. CONCLUSIONS: In CMV endotheliitis, owl's eye cells were observed by specular microscopy with high probability (82%). Corneal endothelial cells significantly decreased when owl's eye cells were observed by specular microscopy. Specular microscopy represents a useful noninvasive auxiliary tool for diagnosing and monitoring CMV corneal endotheliitis.

Relationship between vitreoretinal lymphoma and the site of lymphoma development in the central nervous system.

PURPOSE: To investigate diffuse large B-cell lymphoma lesions with central nervous system (CNS) involvement in patients with vitreoretinal lymphoma (VRL) during long-term clinical courses. STUDY DESIGN: Multicenter, retrospective, and observational research. METHODS: Seventy-one patients participated in this study, 45 were newly diagnosed VRL patients with CNS involvement initially or during follow-up of at least 12 months. We identified the CNS lesions in the patients that had VRL and investigated whether the onset sites of the CNS lesions were associated with the VRL lesions or optic pathways. RESULTS: There were 42 patients with bilateral ocular lesions; 29 had unilateral lesions; 26 had incidental CNS lymphomas. Twenty patients developed recurrent CNS lymphoma 1-73 months after VRL diagnosis; 25 patients had no CNS lesions during the follow-up period. Most CNS lesions were in forebrain-originating tissues (95 lesions/total 124 CNS lesions total), followed by hindbrain-originating tissues, especially the cerebellum. Sixty-seven lesions were found in the non-optic pathway or non-visual cortex. CONCLUSION: Over 60% of the VRL patients had CNS lesions. CNS involvement was not associated with the optic pathway or visual cortex, suggesting that clinicians should carefully examine CNS lesions occurring in both forebrain- and hindbrain-originating tissues during a patient's clinical course. Moreover, the CNS lymphomas that manifest as VRL show multifocal tumor development.

Opposite response of lung adenocarcinoma and its choroidal metastases upon ramucirumab plus docetaxel therapy after immunotherapy: a case report.

We report a unique case of advanced non-small cell lung cancer that exhibited the opposite response to its unilateral choroidal metastases upon ramucirumab plus docetaxel treatment. A combination of cisplatin, pemetrexed, and pembrolizumab was administered as first-line treatment, resulting in shrinkage of all the lesions. However, although the patient was continued on a course of pembrolizumab, all the lesions had recurred approximately two months later. Ramucirumab plus docetaxel, administered as sequential treatment, resulted in maintained shrinkage of the choroidal lesions, yet all the other lesions progressed. Ramucirumab may be a suitable therapy for choroidal metastases, especially if administered immediately after immunotherapy.

Acute endophthalmitis and hyphema mimicking pink hypopyon associated with ocular toxocariasis: A case report.

PURPOSE: To report a case of acute endophthalmitis and hyphema mimicking pink hypopyon associated with ocular toxocariasis. OBSERVATIONS: An immunocompetent 56-year-old woman presented to our hospital with a sudden onset and a three-day history of decreased visual acuity in her left eye. There were no known inciting factors for her symptoms; however, she had a history of eating undercooked beef five days prior. On examination, the best-corrected visual acuity of her left eye was light perception and the intraocular pressure was 24 mmHg. Hyphema mimicking pink hypopyon and vitreous opacity suggestive of acute endophthalmitis were observed in her left eye. The patient underwent an emergency pars plana vitrectomy. The intraoperative findings included iridodialysis, severe vitritis, multiple whitish spots on the retina, white sheathed retinal vessels, and whitish peripheral granuloma. The aqueous humor tap and vitreous tap cultures were negative. Blood tests showed elevated eosinophil and total immunoglobulin (Ig) E levels. Enzyme-linked immunosorbent assay of her intraocular fluid showed positive anti-Toxocara canis IgG reactions; the patient was therefore diagnosed with ocular toxocariasis. Subsequent treatment with oral albendazole and prednisone resulted in significant improvement and recovery of visual acuity to 20/12.5. CONCLUSIONS AND IMPORTANCE: Acute endophthalmitis with hyphema mimicking pink hypopyon is a rare clinical presentation of ocular toxocariasis. The findings from this case highlight the importance of suspecting ocular toxocariasis if a patient presents with acute endophthalmitis and hyphema accompanied with peripheral granuloma. Early vitrectomy and subsequent treatment with oral albendazole and prednisone can be effective in visual recovery.

Identification of TIE2 as a susceptibility gene for neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.

PURPOSE: The endothelial and cell-specific angiopoietin-Tie pathway plays an important regulatory role in angiogenesis. In this study, we investigated the associations of the TIE2 (tyrosine kinase, endothelial, TEK) gene with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV), using haplotype-tagging single-nucleotide polymorphisms (SNPs) analysis. METHODS: This study involved totally 2343 subjects, including a Hong Kong Chinese cohort (214 nAMD patients, 236 PCV patients and 433 control subjects), a Shantou Chinese cohort (189 nAMD patients, 187 PCV patients and 531 control subjects) and an Osaka Japanese cohort (192 nAMD patients, 204 PCV patients and 157 control subjects). Thirty haplotype-tagging SNPs in TIE2 were genotyped in the Hong Kong cohort using TaqMan technology. Two SNPs (rs625767 and rs2273717) showing association in the Hong Kong cohort were genotyped in the Shantou and Osaka cohorts. The SNP-disease association of individual and pooled cohorts were analysed. RESULTS: Two SNPs (rs625767 and rs2273717) showed suggestive association with both nAMD and PCV in the Hong Kong cohort. In the meta-analysis involving all the three cohorts, rs625767 showed significant associations with nAMD (p=0.01; OR=0.82, 95% CI 0.70 to 0.96; I2=0%), PCV (p=0.02; OR=0.83, 95% CI 0.71 to 0.97; I2=27%) and pooled nAMD and PCV (p=0.002; OR=0.82, 95% CI 0.72 to 0.93; I2=0%), with low inter-cohort heterogeneities. CONCLUSION: This study revealed TIE2 as a novel susceptibility gene for nAMD and PCV in Japanese and Chinese. Further studies in other populations are warranted to confirm its role.

Cornea Findings of Spectral Domain Anterior Segment Optical Coherence Tomography in Uveitic Eyes of Various Etiologies.

PURPOSE: To evaluate the morphologic appearance of keratic precipitates (KPs) with spectral domain anterior segment optical coherence tomography (AS-OCT) for the diagnosis of uveitic eyes of various etiologies. METHODS: In all, 153 eyes of 153 patients with different types of uveitis were examined to investigate the morphologic appearance of KPs. The study included 63 eyes with herpetic iridocyclitis/endotheliitis, 58 eyes with ocular sarcoidosis, 5 eyes with Fuchs heterochromic iridocyclitis, and 27 eyes with masquerade syndrome with primary intraocular lymphoma (PIOL). AS-OCT was used to analyze the different KP types among various uveitic groups. RESULTS: KPs were observed in 30 eyes (51.7%) from the ocular sarcoidosis group and in 15 eyes (55.6%) from the PIOL group. In the herpetic iridocyclitis/endotheliitis group, all cases showed KPs (16 cases were positive for herpes simplex virus, 22 cases for varicella zoster virus, and 27 cases for cytomegalovirus). The reflectivity and morphology of the KPs in the AS-OCT images demonstrated different patterns depending on the causative virus. Hemispheric and relatively large KPs were observed in ocular sarcoidosis cases. KPs with Fuchs heterochromic iridocyclitis appeared as small dots. By contrast, relatively high-intensity and dense KPs were observed in PIOL cases. The morphologic features of the KPs in different types of uveitis also showed other patterns such as hemispheric and rectangular-shaped KPs protruding from the retrocornea. CONCLUSIONS: AS-OCT images showed characteristic and specific morphological patterns. AS-OCT examination is a noninvasive and repeatable method for the diagnosis of uveitis by evaluating the morphologies of KPs and treatment effectiveness.

Conjunctival dysbiosis in mucosa-associated lymphoid tissue lymphoma.

To investigate the conjunctival microbiota and the association between the development of conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma and dysbiosis, DNA samples were collected from 25 conjunctival MALT lymphoma patients and 25 healthy controls. To compare the microbiota, samples were collected from the following four body locations: conjunctiva, meibomian gland, periocular skin and hand. Extracted DNA was analyzed by 16S rRNA sequences, and libraries were sequenced on an Illumina MiSeq sequencer. The differences in bacteria were characterized by using principal coordinate analysis of metagenomics data, and the differences in bacterial compositions were evaluated by linear discriminant analysis effect size. The conjunctival microbiota of MALT lymphoma patients was compositionally different from that of healthy controls. For the conjunctival MALT lymphoma patients, alterations in the microbial composition were detected, and a remarkable change was detected at the conjunctiva. Detailed analysis showed that a specific population of the microbiota, the genus Delftia, was significantly more abundant in conjunctival MALT lymphoma patients, and the genera Bacteroides and Clostridium were less abundant in the MALT lymphoma patients. A specific microbiota on the ocular surface in conjunctival MALT lymphoma patients was detected, and dysbiosis may play an important role in the pathophysiology of conjunctival MALT lymphoma.

Rare Histological Type of Adenoma of the Nonpigmented Ciliary Epithelium.

We report the rare case of an adenoma of the nonpigmented ciliary epithelium (NPCE). A 67-year-old healthy man presented with a regularly shaped and nonpigmented mass at the iris root of his right eye. His best-corrected visual acuity was 1.5 with normal intraocular pressure. During observation, the size of the tumor remained stable for 1.5 years but then rapidly grew, extending through the iris, and gradually enlarged to the point of compressing the iris. Ultimately, an iridocyclectomy with scleral resection under a lamellar scleral flap was performed. The histopathologic features of the resected tissue were consistent with adenoma of the NPCE. Histopathological analysis showed that the tumor consisted of both tubular and solid components. There were solid lesions inside of the ciliary epithelium and tubular lesions outside. We observed positive immunoreactivity to vimentin and cytokeratin CK (AE1/AE3) and negative reactivity to S-100 and CD68, both rarely associated with adenoma of NPCE. During 1 year of follow-up after the iridocyclectomy, no signs of tumor recurrence were observed.

Chronological Observations of Iris Flocculi in a Japanese Family with Thoracic Aortic Aneurysm and Dissections.

Iris flocculi, a type of hereditary iris pigment epithelial cyst, have been reported in association with smooth muscle α-2 actin (ACTA2) gene as the causative gene of familial thoracic aortic aneurysm and dissections (FTAAD). The purpose of the report was to examine morphological changes in the shape of flocculi and iris features over time by comparing infants to adults with FTAAD combined with iris flocculi. A Japanese family with FTAAD and bilateral iris flocculi and the Arg149Cys gene mutation was included. A slit-lamp photograph and anterior segment optical coherence tomography (AS-OCT) were used to evaluate the structure and location of iris flocculi. AS-OCT was also used to measure the internal shape and iris thickness of the dilated pupil muscle. A morphological change in the cyst was confirmed to be existent in the youngest cases. Pigment discoloration and iris atrophy of the iris body were observed in all cases. Besides, a decrease in iris thickness was observed with AS-OCT measurement. Changes across generations in iris flocculi occurred in a Japanese family with TAAD. ACTA2 gene abnormalities may cause iris atrophy and decrease thickness in addition to iris flocculi in early life. The prognosis is poor when FTAAD is combined with iris flocculi, and prevention of cardiovascular disease is necessary based on earlier findings of its emergence.

Diagnostic evaluation of optical coherence tomography angiography and fundus autofluorescence in bilateral diffuse uveal melanocytic proliferation.

PURPOSE: To demonstrate the utility of optical coherence tomography angiography (OCTA) in visualizing the choroidal vasculature in bilateral diffuse uveal melanocytic proliferation (BDUMP), so as to elucidate pathophysiology and also aid in diagnosis. Additionally, to recommend autofluorescence (AF) over traditional angiography for purposes of noninvasive diagnosis. OBSERVATIONS: Three BDUMP cases are examined using AF, and two are examined using OCTA. Additionally, the cases vary in etiology and include a case with iris cysts, which we believe to have only been recorded once before in scientific literature, steroids were successfully used to treat two cases and anti-tumor drugs were used to treat the third case. OCTA revealed altered choroidal vasculature in the two cases tested, and AF was successfully used to diagnose all three cases regardless of etiology. CONCLUSIONS AND IMPORTANCE: We believe the OCTA findings are potentially elucidative regarding the pathophysiology at the choroidal layer, where BDUMP lesions primarily exist. Given the limited number of recorded BDUMP cases and relatively unknown pathophysiology, OCTA may prove to be invaluable in visualizing disease progression. Also we were able to use AF to diagnose all three cases ranging from extremely rare iris cysts to a more conventional presentation, indicating its utility regardless of etiology.

Corneal infiltration and xanthoma formation in mycosis fungoides.

PURPOSE: To report a case of corneal infiltration and xanthoma formation in mycosis fungoides (cutaneous T-cell lymphoma). OBSERVATIONS: A middle aged Japanese man with mycosis fungoides (MF) involving the face was referred to Ophthalmology for evaluation of unilateral, painless conjunctival injection. Biopsy of the conjunctiva revealed a malignant T cell population consistent with MF tumor invasion. Years later, he returned following several episodes of infectious keratitis with a painless, yellow, rapidly forming mass in the left eye over two weeks. Corneal biopsy showed foamy histiocytes and positive staining for CD68, and a diagnosis of corneal xanthoma was made. CONCLUSIONS AND IMPORTANCE: Severe ocular surface disease can rarely occur in MF by direct invasion of tumor cells. Corneal infiltration and xanthoma development may be avoidable by careful monitoring for infectious keratitis in patients with conjunctival involvement, as in our case.

Hemorrhagic hypopyon as presenting feature of intravascular lymphoma, a case report.

BACKGROUND: Herpes uveitis has been previously reported to present with hyphema, but hemorrhagic hypopyon is rarely reported as a herpetic uveitis manifestation. We report a case of herpes simplex virus (HSV) presenting with hemorrhagic hypopyon, and speculate on the underlying pathophysiology with relation to an intravascular lymphoma which was subsequently diagnosed as a result. CASE PRESENTATION: We present a case wherein a 62-year-old Japanese rheumatoid arthritis woman, with HSV uveitis, presented with hemorrhagic hypopyon in the anterior chamber and a fever with photophobia. Patient was treated with antiviral drugs which improved the hyphema and corneal lesions, but lesions recurred 3 months later. This rare presentation of HSV induced uveitis, and its subsequent recurrence, aroused suspicion of an additional hypopyon-inducing pathology. On account of previous history of lung opacities and elevated LDH, intravascular lymphoma was eventually diagnosed via lung biopsy. She was treated for the lymphoma which also completely resolved all ocular symptoms without any recurrence as of 1.5 years later. CONCLUSION: The exceedingly rare presentation of hemorrhagic hypopyon may have been enabled by an interaction of the HSV with the intravascular lymphoma. HSV involvement was indicated by the dendritic lesions, IgG assay, and response to anti-viral drugs. The ocular involvement of the intravascular lymphoma seems to be indicated by virtue of the anti-tumor drugs completely resolving all ocular symptoms.

Identification of ANGPT2 as a New Gene for Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy in the Chinese and Japanese Populations.

Purpose: We determine the angiopoietin 2 (ANGPT2) gene as a new susceptibility gene for neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). Methods: A total of 34 haplotype-tagging single-nucleotide polymorphisms (SNPs) were first genotyped in an exploratory Hong Kong Chinese cohort. Suggestive SNPs were replicated in a Shantou Chinese cohort and an Osaka Japanese cohort, with a total of 2343 subjects. The SNP rs800292 in the complement factor H (CFH) gene was genotyped in all the subjects. Genetic association and gene-gene interaction were analyzed. Results: In the Hong Kong cohort, four SNPs in ANGPT2 (rs13255574, rs4455855, rs13269021, and rs11775442) were nominally associated with nAMD and PCV. The four ANGPT2 SNPs showed the same trends of association in the Shantou and Osaka cohorts. Combining the data from the 3 study cohorts revealed that SNPs rs4455855 and rs13269021 achieved study-wise significance (P < 0.0016), conferring an approximately 1.3-fold of increased risk for nAMD and PCV. Interaction analysis revealed the CFH SNP rs800292 has a highly significant interaction with the ANGPT2 SNP rs13269021 in nAMD and PCV in the combined analysis. Subsequent stratification analysis confirmed the interaction. Conclusions: This study reveals ANGPT2 as a new susceptibility gene for nAMD and PCV, and it may affect disease susceptibility in association with CFH. Thus, this report provides new insights into the genetic architecture of nAMD and PCV.