Severe Intraocular Inflammation Following Intravitreal Faricimab.

Importance: Monitoring for and reporting potential cases of intraocular inflammation (IOI) in clinical practice despite limited occurrences in clinical trials, including experiences with relatively new intravitreal agents, such as brolucizumab, pegcetacoplan, or faricimab, helps balance potential benefits and risks of these agents. Objective: To provide descriptions of 3 initially culture-negative cases of acute, severe, posterior-segment IOI events occurring within the same month following intravitreal faricimab injections at a single institution. Design, Setting, and Participants: In this case series, 3 patients manifesting acute, severe IOI following intravitreal injection of faricimab were identified between September 20, 2023, and October 20, 2023. Exposure: Faricimab, 6 mg (0.05 mL of 120 mg/mL solution), for neovascular age-related macular degeneration among patients previously treated with aflibercept; 1 patient also had prior exposure to bevacizumab. Main Outcomes and Measures: Visual acuity, vitreous taps for bacterial or fungal cultures, and retinal imaging. Results: All 3 patients received intravitreal faricimab injections between September 20 and October 20, 2023, from 2 different lot numbers (expiration dates, July 2025) at 3 locations of 1 institution among 3 of 19 retina physicians. Visual acuities with correction were 20/63 OS for patient 1, 20/40 OD for patient 2, and 20/20 OS for patient 3 prior to injection. All 3 patients developed acute, severe inflammation involving the anterior and posterior segment within 3 to 4 days after injection, with visual acuities of hand motion OS, counting fingers OD, and hand motion OS, respectively. Two patients were continuing faricimab treatment while 1 patient was initiating faricimab treatment. All received intravitreal ceftazidime, 2.2 mg/0.1 mL, and vancomycin, 1 mg/0.1 mL, immediately following vitreous taps. All vitreous tap culture results were negative. One patient underwent vitrectomy 1 day following presentation. Intraoperative vitreous culture grew 1 colony of Staphylococcus epidermidis, judged a likely contaminant by infectious disease specialists. All symptoms resolved within 1 month; visual acuities with correction were 20/100 OS for patient 1, 20/50 OD for patient 2, and 20/30 OS for patient 3. Conclusions and Relevance: In this case series, 3 patients with acute, severe IOI within 1 month at 3 different locations among 3 ophthalmologists of 1 institution following intravitreal faricimab could represent some unknown storage or handling problem. However, this cluster suggests such inflammatory events may be more common than anticipated from faricimab trial reports, emphasizing the continued need for vigilance to detect and report such cases following regulatory approval.

Clinical and pathological findings in five dogs with nodular histiocytic iritis in the United Kingdom: A case series.

PURPOSE: The aim of this study was to describe the clinical presentation, histopathology, management, and outcome of nodular histiocytic iritis, an intraocular variant of nodular granulomatous episcleritis (NGE). METHODS: A retrospective review of the medical records of five dogs with intraocular NGE-type inflammation as diagnosed by histopathology. RESULTS: Four Border Collies and one crossbreed dog, aged 1.5-3.4 years (mean age 2.38 years). The clinical presentation was an extensive, raised, pale iris lesion of variable location. All cases were unilateral. The physical examination was normal. Complete blood count/serum biochemistry (n = 1) and thoracic radiography (n = 1) were normal. Ocular ultrasound (n = 2) was normal apart from increased iris thickness. Enucleation (n = 4) or excisional biopsy (iridectomy, n = 1) was performed because of suspected neoplasia. Following enucleation, the remaining, contralateral eye did not develop additional lesions (9 days-3.7 years follow-up). There was no recurrence following sector iridectomy with 5 months topical 1% prednisolone acetate (3.9 years follow-up). The histopathologic findings in all five cases indicated a focal histiocytic and lymphoplasmacytic anterior uveitis (iritis), similar to that seen in cases of NGE. CONCLUSION: Nodular histiocytic iritis presents as unilateral iris thickening in isolation and young Collies appear to be predisposed. The histopathological findings are similar to NGE. Although the clinical presentation resembles intraocular neoplasia, an inflammatory process should be considered, which may be amenable to medical management. Definitive diagnosis may be obtained by iris sampling.

Rubella virus-associated uveitis at a tertiary care hospital in Germany between 2013 and 2019.

Uveitis is a process of intraocular inflammation that may involve different sections of the uveal tract. Apart from systemic or localized immune-mediated diseases, infections are key players in the etiology of uveitis and entail different treatment strategies. Rubella virus (RuV) is a recognized causative agent for the development of Fuchs uveitis, representing a major cause of virus-associated intraocular inflammation. A cohort of 159 patients diagnosed with different forms of uveitis between 2013 and 2019 was subjected to diagnostic antibody testing of the aqueous or vitreous humor. The diagnostic panel included RuV, cytomegalovirus, herpes simplex virus, varicella-zoster virus, and toxoplasmosis. Within this cohort, 38 RuV-associated uveitis (RAU) patients were identified based on a pathologic Goldman-Witmer coefficient indicative of an underlying RuV infection. With a mean age of 45.9 years, the RAU patients were younger than the non-RAU patients (56.3, p < 0.001). The evaluation of clinical parameters revealed a predominance of anterior uveitis and late sequalae such as cataract and glaucoma among the RAU patients. In 15 of the patients a history of prior RuV infections could be confirmed. The study underlines the importance of long-term surveillance of RuV associated diseases that originate from infections before the introduction of RuV vaccination programs.

INTRAOCULAR INFLAMMATION INCIDENCE AFTER INTRAVITREAL BROLUCIZUMAB INJECTION FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

PURPOSE: We evaluated the clinical outcomes of intraocular inflammation (IOI) of eyes with neovascular age-related macular degeneration (AMD) injected with brolucizumab in our tertiary referral center. METHODS: A retrospective case series for which clinical records of all eyes that received intravitreal brolucizumab at Bascom Palmer Eye Institute between December 1, 2019, and April 1, 2021, were reviewed. RESULTS: There were 345 eyes of 278 patients who received 801 brolucizumab injections. IOI was detected in 16 eyes of 13 patients (4.6%). In those patients, baseline Logarithm of Minimu Angle of Resolution (logMAR) best-corrected visual acuity was 0.32 0.2 (20/42), while it was 0.58 0.3 (20/76) at IOI presentation. The mean number of injections among eyes experiencing IOI was 2.4, and the interval between the last brolucizumab injection and IOI presentation was 20 days. There was no known case of retinal vasculitis. Management of IOI included topical steroids in seven eyes (54%), topical and systemic steroids in five eyes (38%), and observation in one eye (8%). Best-corrected visual acuity returned to baseline and inflammation resolved in all eyes by the last follow-up examination. CONCLUSION: Intraocular inflammation after brolucizumab injection for neovascular AMD was not uncommon. Inflammation resolved in all eyes by the last follow-up visit.

UVEAL EFFUSION ASSOCIATED WITH LOCALIZED SCLERODERMA BECAUSE OF SCLERAL FIBROSIS.

BACKGROUND/PURPOSE: To report a case of uveal effusion associated with localized scleroderma because of scleral collagen fibrosis. Partial-thickness sclerectomy treatment was successful in acquiring the resolution of the uveal effusion. METHODS: Case report. RESULTS: A 44-year-old Chinese woman with known localized scleroderma visited the retinal clinic complaining of insidious onset blurring of vision in both eyes for 8 months. The best-corrected visual acuity was 20/200. Ophthalmoscopy revealed apparent inferior bullous serous retinal detachments in the right eye. Optical coherence tomography showed subretinal fluid and folds of the retinal pigment epithelium layer in both eyes. B-scan ultrasonographic image of the right eye confirmed a 360-degree serous retinal detachment in the right eye accompanied with increased thickness of the ocular wall. Ultrasound biomicroscopy of the anterior segment detected a shallow ciliary body detachment in the right eye. Fluorescein angiography and indocyanine green angiography demonstrated the leopard-spot pattern in all phases. Partial-thickness sclerectomy treatment was successful in acquiring the resolution of the uveal effusion. Histopathologic examinations of the sclera flaps revealed scleral collagen fibrosis. CONCLUSION: This clinicopathologic report first describes a patient with localized scleroderma and scleral collagen fibrosis, resulting in uveal effusion that responded to partial-thickness sclerectomy.

Heavy Silicone Oil as an Endotamponade in Recurrent or Complicated Retinal Detachment and Macular Hole

Objectives: To evaluate the efficacy and safety of heavy silicone oil as an endotamponade in patients with recurrent or complicated retinal detachment and macular hole. Materials and Methods: Nineteen eyes of 19 patients who underwent heavy silicone oil endotamponade for different indications were included in the study and evaluated by retrospective chart review. At each visit, patients underwent detailed ophthalmological examination and anatomical and functional outcomes, silicone oil emulsification, intraocular inflammation, presence of proliferative vitreoretinopathy, preoperative and postoperative visual acuity, and postoperative complications were recorded. Results: The study included 19 eyes of 19 consecutive patients: 13 women (68.4%) and 6 men (31.6%). The patients' median age was 60 years (interquartile range [IQR]: 44-70 years) and the median follow-up time was 19 months (IQR: 9-31 months). Indications for heavy silicone oil endotamponade were recurrent retinal detachment in 11 eyes (57.8%), inferior retinal detachment in 5 eyes (26.3%), inferior rhegmatogenous retinal detachment, recurrent macular hole in 2 patients (10.5%), and macular hole in 1 patient (5.2%). Median best corrected visual acuity was 2 logMAR (IQR: 1-2.6) preoperatively and 0.99 logMAR (IQR: 0.4-2) postoperatively (p<0.001). Postoperative anatomical success was achieved in all patients. Densiron 68 was used for endotamponade in 14 patients (73.7%), Densiron XTRA in 3 patients (15.8%), and AlaHeavy 1.07 in 2 patients. Heavy silicone oil emulsification was observed in only 3 patients (15.8%). Conclusion: Although heavy silicone oil has limitations as an endotamponade, such as intraocular pressure increase, emulsification, intraocular inflammation, and the risk of complications during removal, it is a safe and effective alternative in eyes requiring inferior retinal tamponade for indications like proliferative vitreoretinopathy and recurrent macular holes.

Uveal Effusion Associated with Presumed Viral Encephalitis.

BACKGROUND: Uveal effusion is a rare disease that is characterized by exudative detachment of the ciliary body and choroid. Herein, we report a rare case of uveal effusion associated with viral encephalitis, which resolved following the treatment of the viral encephalitis and administration of corticosteroids. CASE PRESENTATION: A 67-year-old man who was hospitalized for viral encephalitis was referred to our clinic. He had been treated for herpes zoster ophthalmicus in his left eye 3 weeks previously. Choroidal detachment and uveal effusion between the ciliary body and sclera were observed. He was prescribed oral and topical steroids and cycloplegics to treat uveal effusion, and an antiviral agent (Acyclovir) to treat viral encephalitis. After 4 weeks, the choroidal detachment resolved completely. CONCLUSIONS: Uveal effusion syndrome can develop in association with viral encephalitis and be treated successfully with oral and topical steroids; we suggest that medical treatment should be attempted prior to surgery. ABBREVIATIONS: ADEM: Acute disseminated encephalomyelitis; BCVA: Best corrected visual acuity; CSF: Cerebrospinal fluid; CT: Computed tomography; MRI: Magnetic resonance imaging; WBC: White blood cell.

IDIOPATHIC PENETRATION OF CILIA INTO THE POSTERIOR SEGMENT PRESENTING AS SECTORAL SCLERITIS WITH PROGRESSIVE INTRAOCULAR INFLAMMATION.

PURPOSE: To report two cases of idiopathic intraocular cilia presenting as sectoral scleritis with progressive intraocular inflammation. METHODS: Both patients were treated with intravitreal antibiotics and underwent pars plana vitrectomy where the cilia were removed and identified on histopathology. RESULTS: One patient developed a retinal detachment while being treated for presumed endophthalmitis. The intraocular cilium was discovered during pars plana vitrectomy. In the second case, the cilium was detected on dilated fundus exam and was believed to be the cause of the patient's scleritis and vitritis. Therapeutic vitrectomy was performed. In both cases, the cilia were positively identified on histopathology. CONCLUSION: Idiopathic intraocular penetration of cilia should be considered in the differential diagnosis of sectoral scleritis with progressive intraocular inflammation.

Visual outcome of endogenous endophthalmitis in Thailand.

To evaluate a 10-year visual outcome of endogenous endophthalmitis (EE) patients. A 10-year retrospective chart review of EE patients. Thirty-eight patients (40 eyes) were diagnosed with EE at the mean age of 42. Among the identifiable pathogens (71.1% culture positive), the causative agents were predominantly gram-negative bacteria (48.1%). The most common specie was Klebsiella pneumoniae (25.9%). About a quarter of the patients required surgical eye removal, and the remaining 45.7% had visual acuity (VA) worse than hand motion at one month after the infectious episode. The most common complication was ocular hypertension (52.5%). Poor initial VA was significantly associated with a worse visual outcome in the early post-treatment period (p 0.12, adjusted OR 10.20, 95% CI 1.65-62.96). Five patients continued to visit the clinic for at least ten years. One patient had gained his vision from hand motion to 6/7.5. Two patients had visual deterioration, one from corneal decompensation, and the other from chronic retinal re-detachment. Two patients developed phthisis bulbi, with either some VA perception of light or no light perception. Poor initial VA is the only prognostic factor of a poor early post-treatment visual outcome of EE.

Bilateral diffuse uveal melanocytic proliferation: Report of a rare Ocular Paraneoplastic Syndrome.

Bilateral diffuse uveal melanocytic proliferation is a rare paraneoplastic disorder where bilateral blindness is caused by uveal thickening, serous retinal detachment, and rapid cataract formation. Several different malignancies have been associated with bilateral diffuse uveal melanocytic proliferation, but ovarian carcinoma in women and lung and pancreatic carcinoma in men are the most common. The underlying mechanism is thought to be related to a an endogenous factor wich regulates the proliferation of uveal melanocytes. We present the case of a 75-year-old man with bilateral diffuse uveal melanocytic proliferation secondary to pulmonary adenocarcinoma.

[Bilateral diffuse uveal melanocytic proliferation : a rare paraneoplasic syndrome to be diagnosed early]. / Cas clinique. Prolifération mélanocytique uvéale bilatérale diffuse : un syndrome paranéoplasique rare à reconnaître précocement.

Diffuse bilateral uveal melanocytic proliferation is a rare paraneoplastic ophthalmologic syndrome. The increase in life expectancy in oncology partly explains the gradual increase in its incidence. In almost half of the cases, the syndrome manifests itself before the diagnosis of primary neoplasia. It should be suspected in cases of bilateral uveal pigmented lesions that do not meet the clinical criteria for other known eye pathologies. Legal blindness occurs for the majority of patients during the first year after the initial clinical presentation. Death, due to the severity of the underlying pathology, occurs statistically within three years. Here we display the case of such a diffuse bilateral uveal melanocytic proliferation in a patient with relapsed colonic adenocarcinoma, initially treated for age-related macular degeneration.

La prolifération mélanocytique uvéale bilatérale diffuse est un syndrome paranéoplasique ophtalmologique rare. L'augmentation de l'espérance de vie en oncologie explique, en partie, la majoration progressive de son incidence. Dans près de la moitié des cas, le syndrome se manifeste antérieurement au diagnostic de la néoplasie primaire. Il doit être suspecté en cas de lésions pigmentées uvéales bilatérales ne répondant pas aux critères cliniques d'autres pathologies oculaires connues. La cécité légale s'établit chez la majorité des patients durant la première année suivant la présentation clinique initiale. Un décès, dû à la sévérité de la pathologie sous-jacente, survient presque toujours dans les trois ans. Nous rapportons ici le cas d'une telle prolifération mélanocytique uvéale bilatérale diffuse, chez une patiente atteinte d'un adénocarcinome colique en rechute, traitée initialement pour une dégénérescence maculaire liée à l'âge.

Nanophthalmos-Associated MYRF Gene Mutation Causes Ciliary Zonule Defects in Mice.

Purpose: Patients with nanophthalmos who undergo intraocular surgery often present with abnormal ciliary zonules. In a previous study, we reported mutation in MYRF that is implicated in the pathogenesis of nanophthalmos. The aim of this study was to model the mutation in mice to explore the role of MYRF on zonule structure and its major molecular composition, including FBN1 and FBN2. Methods: Human MYRF nanophthalmos frameshift mutation was generated in mouse using the CRISPR-Cas9 system. PCR and Sanger sequencing were used for genotype analysis of the mice model. Anterior chamber depth (ACD) was measured using hematoxylin and eosin-stained histology samples. Morphologic analysis of ciliary zonules was carried out using silver staining and immunofluorescence. Transcript and protein expression levels of MYRF, FBN1, and FBN2 in ciliary bodies were quantified using quantitative real-time PCR (qRT-PCR) and Western blot. Results: A nanophthalmos frameshift mutation (c.789delC, p.N264fs) of MYRF in mice showed ocular phenotypes similar to those reported in patients with nanophthalmos. ACD was reduced in MYRF mutant mice (MYRFmut/+) compared with that in littermate control mice (MYRF+/+). In addition, the morphology of ciliary zonules showed reduced zonular fiber density and detectable structural dehiscence of zonular fibers. Furthermore, qRT-PCR analysis and Western blot showed a significant decrease in mRNA expression levels of MYRF, FBN1, and FBN2 in MYRFmut/+ mice. Conclusions: Changes in the structure and major molecular composition of ciliary zonules accompanied with shallowing anterior chamber were detected in MYRFmut/+ mice. Therefore, MYRF mutant mice strain is a useful model for exploring pathogenesis of zonulopathy, which is almost elusive for basic researches due to lack of appropriate animal models.

Atypical free-floating iridociliary pigmented epithelial cysts and secondary glaucoma in a caiman (Caiman latirostris).

We describe a case of chronic ocular trauma that resulted in fixed and free-floating, pigmented epithelial iridociliary cysts, inflammation, and secondary glaucoma in a caiman (Caiman latirostris). A 20- to 25-year-old male caiman was presented with phthisis bulbi in the right eye, and congested episcleral vessels, corneal leukoma, disorganized anterior chamber, multifocal anterior synechia, and elevated intraocular pressure in the left eye. Ocular ultrasound of the left eye revealed round structures dispersed in the anterior and posterior chambers and vitreous cavity. Bilateral enucleation was performed, and gross pathology of the left eye revealed multiple pigmented cysts attached to the iris and posterior corneal surface causing marked distortion of the anterior uvea, and free-floating in the vitreous cavity. Histopathology demonstrated heavily pigmented cystic structures of iridociliary epithelium origin carpeting the anterior segment surfaces and causing obstruction of the iridocorneal angles, leading to secondary glaucoma. To the authors' knowledge, this is the first report of iridociliary cysts in wildlife species.