Rd9 Is a Naturally Occurring Mouse Model of a Common Form of Retinitis Pigmentosa Caused by Mutations in RPGR-ORF15

Animal models of human disease are an invaluable component of studies aimed at understanding disease pathogenesis and therapeutic possibilities. Mutations in the gene encoding retinitis pigmentosa GTPase regulator (RPGR) are the most common cause of X-linked retinitis pigmentosa (XLRP) and are estimated to cause 20% of all retinal dystrophy cases. A majority of RPGR mutations are present in ORF15, the purine-rich terminal exon of the predominant splice-variant expressed in retina. Here we describe the genetic and phenotypic characterization of the retinal degeneration 9 (Rd9) strain of mice, a naturally occurring animal model of XLRP. Rd9 mice were found to carry a 32-base-pair duplication within ORF15 that causes a shift in the reading frame that introduces a premature-stop codon. Rpgr ORF15 transcripts, but not protein, were detected in retinas from Rd9/Y male mice that exhibited retinal pathology, including pigment loss and slowly progressing decrease in outer nuclear layer thickness. The levels of rhodopsin and transducin in rod outer segments were also decreased, and M-cone opsin appeared mislocalized within cone photoreceptors. In addition, electroretinogram (ERG) a- and b-wave amplitudes of both Rd9/Y male and Rd9/Rd9 female mice showed moderate gradual reduction that continued to 24 months of age. The presence of multiple retinal features that correlate with findings in individuals with XLRP identifies Rd9 as a valuable model for use in gaining insight into ORF15-associated disease progression and pathogenesis, as well as accelerating the development and testing of therapeutic strategies for this common form of retinal dystrophy

Retinochoroiditis secondary to Rickettsia typhi infection: a case report

Abstract Background To report a case of unusual presentation of retinochoroiditis caused by Rickettsia typhi in a patient without prior uveitis. Case presentation In this case, we describe a 24-year-old male soldier with no previous eye disease, who was referred to our ophthalmology department due to bilateral retinochoroiditis and vitritis. The patient initially presented with a paracentral scotoma in his right eye persisting for 7 days and scattered dark spots in his left eye for 2 days in June 2023. Preceding these ocular symptoms, he experienced a two-week episode of fever, headaches, night sweats, and rapid weight loss of 10 kg. A transient rash covered his body briefly. His mother had a history of recurrent eye inflammation. Physical examination revealed bilateral keratic precipitates on the lower corneal periphery, 1 + anterior vitreous cells, small retinal lesions and mild optic discs elevation. Fluorescein angiography indicated mild discs hyperfluorescence, and the clinically visible round punctate lesions on OCT showed inner retinal hyper-reflective lesion with a depth till outer plexiform layer possibly suggestive of a retinitis lesion. Laboratory tests were normal except thrombocytosis, elevated ESR, liver enzymes and ACE levels, with positive Rickettsia typhi serology tests. Rheumatology and infectious disease consultations ruled out autoimmune diseases, confirming Rickettsia typhi infection. Treatment included systemic doxycycline and prednisone, with improvement of visual acuity, ocular symptoms, OCT abnormalities and resolution of inflammation. Prednisone was discontinued, and after two months, additional improvement was seen clinically, with preserved retinal structures on OCT. Conclusion This study explores retinochoroiditis as a rare ocular presentation of Rickettsia typhi, an unusual infection in the Middle East. Previously reported ocular manifestations include conjunctivitis, vitritis, post infectious optic neuropathy and a few cases of uveitis. Ocular symptoms followed systemic illness, highlighting the need for awareness among clinicians. Diagnosis relies on seroconversion, with fluorescein angiography and OCT aiding in assessment. Empiric doxycycline and systemic corticosteroid therapy is recommended. Ocular symptoms resolved in two months. Awareness of these ocular manifestations is essential for timely diagnosis and management. Further research is needed to fully understand this aspect of murine typhus

Ocular Behçet Disease—Clinical Manifestations, Treatments and Outcomes According to Age at Disease Onset

Behçet disease (BD) is a multisystemic disease that commonly involves the eyes. Although it affects patients in all age groups, data on ocular disease by age of onset are limited. This retrospective, multicenter study aimed to compare epidemiology, systemic and ocular manifestations, treatments and outcomes between three age groups: juvenile (n = 25, 14.3%), adult-onset (n = 120, 68.6%) and late-onset (n = 30, 17.1%). Most patients in all groups were male. Systemic manifestations were similar in all groups. Systemic co-morbidities were more common in late-onset patients. Bilateral panuveitis was the most common ocular manifestation in all patients. Non-occlusive retinal vasculitis, peripheral vessel occlusions, cataract and elevated intraocular pressure were found more commonly among juvenile-onset eyes. Anterior uveitis and macular ischemia were most common among late-onset eyes, while branch retinal vein occlusion was most common in adult and late-onset eyes. All patients were treated with corticosteroids. Methotrexate, immunomodulatory combinations and biologic treatments were more commonly used for juvenile-onset patients. All groups had a similar visual outcome. Our study showed that patients with ocular BD have varied ocular manifestations and require different treatments according to age of disease onset, but visual outcome is similar