Effectiveness of Baricitinib in Refractory Seronegative Rheumatoid Arthritis and Uveitis: A Case Report

Baricitinib is a Janus kinase (JAK) inhibitor used to treat refractory rheumatoid arthritis and blocks the subtypes JAK1 and JAK2. A 35-year-old man with seronegative rheumatoid arthritis complicated by bilateral severe non-granulomatous panuveitis was resistant to steroid treatment, multiple conventional disease-modifying antirheumatic drugs (methotrexate and salazosulfapyridine), and TNF-α inhibitors (adalimumab and infliximab). Therefore, the TNF-α inhibitors were switched to baricitinib to decrease the activity of systemic arthritis. Along with the amelioration of inflammatory activity in seronegative rheumatoid arthritis, the inflammatory activity of uveitis was decreased. Vitreous opacity, serous retinal detachment, and anterior chamber cells showed improvement. Baricitinib was effective not only in refractory systemic arthritis but also in uveitis, which may provide a new treatment option for patients with refractory uveitis.

Novel BMP4 Truncations Resulted in Opposite Ocular Anomalies: Pathologic Myopia Rather Than Microphthalmia

BMP4 variants have been reported to be associated with syndromic microphthalmia (MCOPS6, OMIM 607932). This study aims to describe BMP4 truncation mutations contributing to a novel phenotype in eight patients from four Chinese families. In this study, BMP4 variants were collected from a large dataset from in-house exome sequencing. Candidate variants were filtered by multiple in silico tools as well as comparison with data from multiple databases. Potential pathogenic variants were further confirmed by Sanger sequencing and cosegregation analysis. Four novel truncation variants in BMP4 were detected in four out of 7,314 unrelated probands with different eye conditions. These four mutations in the four families solely cosegregated in all eight patients with a specific form of pathologic myopia, characterized by significantly extended axial length, posterior staphyloma, macula patchy, chorioretinal atrophy, myopic optic neuropathy or glaucoma, vitreous opacity, and unique peripheral snow-grain retinopathy. The extreme rarity of the truncations in BMP4 (classified as intolerant in the gnomAD database, pLI = 0.96), the exclusive presence of these variants in the four families with pathologic myopia, variants fully co-segregated with the same specific phenotypes in eight patients from the four families, and the association of the pathogenicity of truncations with syndromic microphthalmia in previous studies, all support a novel association of BMP4 truncations with a specific form of pathologic myopia. The data presented in this study demonstrated that heterozygous BMP4 truncations contributed to a novel phenotype: pathologic myopia rather than microphthalmia. Mutations in the same gene resulting in both high myopia and microphthalmia have been observed for a few other genes like FZD5 and PAX6, suggesting bidirectional roles of these genes in early ocular development. Further studies are expected to elucidate the molecular mechanism of the bidirectional regulation.

Recurrent Toxoplasma Retinitis Treated with Long-Term Oral Antibiotics

Purpose: The purpose of this case was to report the inhibition of toxoplasma retinitis reactivation with long-term, low-dose antibiotics.Case summary: A 76-year-old woman complained of poor vision and floaters in her right eye. The corrected visual acuity (LogMAR) of the right eye was 0.5, and there was an area of yellow infiltration and dye leakage on the retinal fluorescein angiography images. Toxoplasma IgG were detected in the serum, the patient was diagnosed with toxoplasma retinitis, and the patient was advised oral trimethoprim-sulfamethoxazole, clindamycin, and steroids. Her visual acuity improved and the inflammation resolved. However, she again had decreased visual activity and retinal inflammation in her right eye after 5 months. The inflammation improved with oral steroids, but she was shifted to intravitreal dexamethasone because of the side effects of systemic steroids. Although the inflammation improved initially, there was worsening of inflammation (evidenced by vitreous opacity) after 2 months, which was treated with oral antibiotics. After vitrectomy for the removal of residual vitreous opacity, antibiotics were stopped because of the stable disease course. After discontinuation of the antibiotics, inflammation was noted again, and low-dose trimethoprim-sulfamethoxazole was administered. Low-dose antibiotics were continued for 5 months and the disease remained stable without any retinal inflammation.Conclusions: Long-term, low-dose oral antibiotics may prevent reactivation of recurrent toxoplasma retinitis.

Gliotic opaque posterior hyaloid membrane separation: report of two cases

Background To report two cases with idiopathic unilateral diffuse opacification of the posterior hyaloid membrane (PHM) completely separated from the retina, the mechanism of which is possibly due to glial cell proliferation and migration. Case presentation Two Japanese women at age 75 and 84 with no systemic or ocular history developed diffuse opacification in one eye resembling a ground glass sheet almost all over the surface of the PHM, but not within the vitreous gel or fluid. The retinas were funduscopically normal; however, optical coherence tomography demonstrated hyperreflective icicle-like anterior protrusions from the surface of the fovea. The patients received pars plana vitrectomy, resulting in visual improvement. Cell block preparations of the vitreous in one case revealed a cluster of cells immunoreactive for glial fibrillary acidic protein in consistence with gliosis, while denying vitreoretinal lymphoma from lack of atypical cells and vitreous amyloidosis due to no staining for Congo red or direct fast scarlet. The lesions did not recur during follow-up with no new funduscopic abnormalities. Conclusions To our knowledge, this is the first to demonstrate such peculiar cases of vitreous opacity with idiopathic and unilateral onset. Histological assessments revealed the possible pathogenesis of gliotic opaque PHM separation to cause its ground-glass-sheet appearance.

Complete and early vitrectomy for endophthalmitis

We recently co-authored a report on the ten-year (2007-2017) results achieved at our center (Retina Specialists of Alabama) in the treatment of Acute Post-Cataract (APCE). Of all eyes, 77.4% were initially treated with Complete and Early Vitrectomy (CEVE). Visual acuity of ≥20/40 was restored in 79% of all eyes versus 53% of eyes reported in the Endophthalmitis Vitrectomy Study. We believe that CEVE is the initial treatment of choice whenever the fundus is obscured by endophthalmitis vitreous opacity.

Fusarium infection complicating rheumatic keratitis that acutely progressed to endophthalmitis during regular infusion of tocilizumab: a case report

Background Filamentous fungi are ubiquitous in plants, water, and soil. The predominant fungi that infect the human cornea include Fusarium and Aspergillus species. The onset of fungal endophthalmitis is indolent, and typically takes weeks to months to develop after corneal infection. We report a case of Fusarium infection complicating rheumatic keratitis that acutely progressed to endophthalmitis during intravenous tocilizumab therapy. Case presentation A 65-year-old female patient was referred to our department due to pain and decreased vision in her left eye. Slit-lamp examination showed a white focus on the upper peripheral cornea, hypopyon, anterior chamber fibrin formation, marked ciliary hyperemia, and whole corneal epithelial defects. As the corneal scraping smear was positive for filamentous fungi and Fusarium species were detected by aqueous humor polymerase chain reaction, anti-fungal therapy was started. Although the initial response to anti-fungal therapy was good, we observed corneal infiltration, worsening hypopyon, and vitreous opacity after tocilizumab infusion. Given that the infection continued to progress despite conservative therapy, we performed penetrating keratoplasty combined with vitrectomy. After removal of the white focus beneath the intraocular lens, a temporary corneal prosthesis was mounted and the dense vitreous opacity was removed. Finally, a frozen donor graft was sutured in place. The corneal infiltration, hypopyon, and vitreous opacity all disappeared after the operation. Conclusion The rapid progression of Fusarium keratitis to endophthalmitis in a patient who was receiving a regular infusion of tocilizumab demonstrates that ocular condition should be closely monitored during systemic tocilizumab administration due to increased risk of infection.

Acute symptomatic vitreous floaters assessed with ultra-wide field scanning laser ophthalmoscopy and spectral domain optical coherence tomography

To describe the eyes with vitreous floaters and to analyze the development of acute symptomatic posterior vitreous detachment (PVD). A retrospective review of medical records was performed on patients with the vitreous floater developed for the first time of their life. Peripapillary vitreous opacity (pVO) was searched in Ultra-wide field (UWF) scanning laser ophthalmoscopy and PVD stage was assessed through spectral-domain optical coherence tomography (SD-OCT). 196 patients (55 males and 141 females), who were 58.4 (± 9.1) years old, visited a retinal clinic 9.4 (± 9.1) days after they experienced vitreous floaters. In 196 eyes, pVO was noticed in 122 eyes (62.2%) at UWF. In 106 eyes where SD-OCT data were available, PVD was noticed in 100 eyes (94.3%). Symptomatic eyes showed more advanced stage of PVD (p < 0.001) than symptom free eyes. Eyes with floaters were more myopic (− 0.7 ± 2.2D vs − 0.5 ± 1.9D, p = 0.02), and had lower intraocular pressure (IOP) (14.7 ± 3.2 mmHg vs 15.2 ± 3.0 mmHg, p = 0.02) than the other symptom free eyes. In patients with first floater symptoms, PVD was in progress in most of the eyes not only the symptomatic eyes but also on the contralateral symptom free eyes. Eyes with vitreous floaters were more myopic and had lower IOP than the opposite symptom free eyes.

Acute Symptomatic Vitreous Floaters Assessed With Ultra-Wide Field Scanning Laser Ophthalmoscopy and Spectral Domain Optical Coherence Tomography

Purpose: To describe the eyes with vitreous floaters and to analyze the development of acute symptomatic posterior vitreous detachment (PVD). Methods: A retrospective review of medical records was performed on patients with the vitreous floater developed for the first time of their life. Peripapillary vitreous opacity (pVO) was searched in Ultra-wide field (UWF) scanning laser ophthalmoscopy and PVD stage was assessed through spectral-domain optical coherence tomography (SD-OCT). Results: 196 patients (55 males and 141 females), who were 58.4(±9.1) on years old, visited a retinal clinic 9.4 (±9.1) days after they experienced vitreous floaters. (pVO) was noticed in 62.2% at UWF and PVD was initiated more than 94.3%. Symptomatic eyes had more prevalence of peripapillary vitreous opacity (63.2% vs 18.4%, p=0.040) and more advance staged PVD (p<0.001) than symptom free eyes. Eyes with floaters were more myopic (-0.7±2.2D vs -0.5±1.9D, p=0.02), and had lower IOP (14.7±3.2mmHg vs 15.2±3.0mmHg, p=0.02) than the other symptom free eyes. Conclusion: In patients with first floater symptoms, PVD was in progress in most of the eyes not only the symptomatic eyes but also on the contralateral symptom free eyes. Eyes with vitreous floaters were more myopic and had lower IOP than the opposite symptom free eyes.

Fab-Nanolipoprotein Conjugate Causes Vitreous Opacity and Cataracts Following a Single Intravitreal Administration in New Zealand White Rabbits

One strategy employed to prolong the ocular half-life of large molecule therapeutics is via covalent attachment to a carrier, resulting in an increase in size thereby slowing their clearance from the eye. Rabbit antigen-binding fragment conjugated to nanolipoprotein (RabFab-NLP) is a novel conjugate intended to prolong ocular half-life through an increase in hydrodynamic radius compared to Fab alone (∼12 vs ∼3 nm). Nanolipoproteins are mimetics of endogenous high-density lipoproteins and consist of lipids and apolipoproteins (ApoE422k), both biologically derived materials. The objective of this study was to evaluate the ocular toxicity and toxicokinetics of RabFab-NLP after a single intravitreal administration in New Zealand White rabbits. Serum toxicokinetic data suggested a significant increase in ocular residence time of RabFab-NLP compared to RabFab alone. Ophthalmic examinations showed that RabFab-NLP caused vitreous and lens opacities as early as day 3 and day 8 postdose, respectively, which persisted for the entire study duration to day 30. The RabFab-NLP-related microscopic findings were present in the lens, vitreous cavity, and/or optic nerve head. Based on the observed ocular toxicity, a single intravitreal dose of 1.3 mg/eye RabFab-NLP was not tolerated and caused vitreous opacity and cataracts in rabbit eyes.