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Purpose Immune checkpoint inhibitors (ICIs) are associated with a range of immune-related adverse ophthalmic events. To date, there are scant reports of ocular hypertension coupled with ICI-associated uveitis. However, in instances of ocular hypertension in the context of only mild uveitic reaction and absence of synechiae, trabeculitis is considered. This series describes our observations of presumed trabeculitis in the setting of ICI therapy and investigates the clinical findings, treatment and outcome of these patients. Observations Two eyes of 2 patients (both male aged 65 and 43) developed a mild anterior uveitis and elevated intraocular pressure (IOP) with open angles and no evidence of peripheral anterior synechiae in association with ICI treatment for their malignancy; and were considered to have presumed unilateral trabeculitis. The patients underwent 10 cycles (6.53 months) and 2 cycles (3.33 months) respectively of ICI therapy before developing ophthalmic symptoms. Neither patient was on systemic or topical steroid treatment at time of diagnosis and there was no suspicion of a viral etiology for the inflammation. Following management, the anterior uveitis resolved and IOP rapidly returned to normal in both eyes: ICI therapy was discontinued in both patients (and uneventfully re-challenged at a lower dose in one patient) and both eyes were treated with a combination of topical and/or oral glaucoma medications and topical steroids. Conclusions and Importance Uveitic ocular hypertension has been described with ICI. However, another immune-related mechanism for ocular hypertension with unique clinical characteristics, includes trabeculitis. We describe two cases of trabeculitis in the setting of ICI-therapy. The intraocular inflammation and elevated intraocular pressure which characterizes trabeculitis often responds rapidly to conservative treatment. In both patients checkpoint inhibitor therapy was discontinued and, in one patient, was re-challenged at a lower dose without recurrence. Immunotherapy is now more widely used for cancer treatment and its potential ocular manifestations should be shared with the ophthalmic community.

Ocular complications due to ZIKV infection remains a major public health concern because of their ability to cause visual impairment or blindness. Most of the previous studies have shown ZIKV-induced ocular pathology in the posterior segment (i.e., retina) of the eye. However, some recent clinical reports from affected countries highlighted the importance of ZIKV in affecting the anterior segment of the eye and causing congenital glaucoma. Because glaucoma is the second leading cause of blindness worldwide, it is imperative to study ZIKV infection in causing glaucoma to identify potential targets for therapeutic intervention. In this study, we discovered that ZIKV permissively infects human TM cells and evokes inflammatory responses causing trabeculitis. Using a mouse model, we demonstrated that ZIKV infection resulted in higher IOP, increased RGC loss, and optic nerve abnormalities, the classical hallmarks of glaucoma. Collectively, our study provides new insights into ocular ZIKV infection resulting in glaucomatous pathology., Zika virus (ZIKV) infection during pregnancy leads to devastating fetal outcomes, including neurological (microcephaly) and ocular pathologies such as retinal lesions, optic nerve abnormalities, chorioretinal atrophy, and congenital glaucoma. Only clinical case reports have linked ZIKV infection to causing glaucoma, a major blinding eye disease. In the present study, we have investigated the role of ZIKV in glaucoma pathophysiology using in vitro and in vivo experimental models. We showed that human primary trabecular meshwork (Pr. TM) cells, as well as a human GTM3 cell line, were permissive to ZIKV infection. ZIKV induced the transcription of various genes expressing pattern recognition receptors (TLR2, TLR3, and RIG-I), cytokines/chemokines (TNF-α, IL-1β, CCL5, and CXCL10), interferons (IFN-α2, IFN-β1, and IFN-γ), and interferon-stimulated genes (ISG15 and OAS2) in Pr. TM cells. ZIKV infection in IFNAR1−/− and wild-type (WT) mouse eyes resulted in increased intraocular pressure (IOP) and the development of chorioretinal atrophy. Anterior chamber (AC) inoculation of ZIKV caused infectivity in iridocorneal angle and TM, leading to the death of TM cells in the mouse eyes. Moreover, anterior segment tissue of infected eyes exhibited increased expression of inflammatory mediators and interferons. Furthermore, ZIKV infection in IFNAR1−/− mice resulted in retinal ganglion cell (RGC) death and loss, coinciding with optic nerve infectivity and disruption of anterograde axonal transport. Because of similarity in glaucomatous pathologies in our study and other experimental glaucoma models, ZIKV infection can be used to study infectious triggers of glaucoma, currently an understudied area of investigation. IMPORTANCE Ocular complications due to ZIKV infection remains a major public health concern because of their ability to cause visual impairment or blindness. Most of the previous studies have shown ZIKV-induced ocular pathology in the posterior segment (i.e., retina) of the eye. However, some recent clinical reports from affected countries highlighted the importance of ZIKV in affecting the anterior segment of the eye and causing congenital glaucoma. Because glaucoma is the second leading cause of blindness worldwide, it is imperative to study ZIKV infection in causing glaucoma to identify potential targets for therapeutic intervention. In this study, we discovered that ZIKV permissively infects human TM cells and evokes inflammatory responses causing trabeculitis. Using a mouse model, we demonstrated that ZIKV infection resulted in higher IOP, increased RGC loss, and optic nerve abnormalities, the classical hallmarks of glaucoma. Collectively, our study provides new insights into ocular ZIKV infection resulting in glaucomatous pathology.

Caso clínico: Varón de 62 años de edad con trasplante renal y tratamiento inmunosupresor que acude por disminución de la visión (20/100) en ojo izquierdo, edema corneal y presión intraocular de 46mmHg. Un mes después aparece queratitis dendrítica marginal inferior. El raspado corneal y la proteína C reactiva demuestran la presencia de un virus del herpes simple (HVS). Discusión: La epiteliopatía corneal autoinmunitaria o endotelitis idiopática corneal se caracteriza por edema corneal y precipitados queráticos. Se cree que el HVS podría ser secretado desde el trabeculum, inervado por el nervio trigémino, apoyado clínicamente por la progresión del edema estromal desde la periferia. Case report: A 62-year-old man with previous renal transplant and immunosuppressive treatment presented with decreased visual acuity (20/100) in his left eye, corneal oedema and intraocular pressure of 46mmHg. One month later an inferior marginal dendritic keratitis appeared. Corneal scraping and real-time polymerase chain reaction showed herpes simplex virus (HSV). Discussion: The autoimmune corneal endotheliopathy or acute idiopathic corneal endotheliitis is characterised by corneal stromal oedema and keratic precipitates. HSV might be secreted from the trabeculum, innervated by the trigeminal nerve. This hypothesis is supported by the clinical observation that the corneal stromal oedema usually starts from the periphery.

Resumen Caso clinico Varon de 62 anos de edad con trasplante renal y tratamiento inmunosupresor que acude por disminucion de la vision (20/100) en ojo izquierdo, edema corneal y presion intraocular de 46 mmHg. Un mes despues aparece queratitis dendritica marginal inferior. El raspado corneal y la proteina C reactiva demuestran la presencia de un virus del herpes simple (HVS). Discusion La epiteliopatia corneal autoinmunitaria o endotelitis idiopatica corneal se caracteriza por edema corneal y precipitados queraticos. Se cree que el HVS podria ser secretado desde el trabeculum, inervado por el nervio trigemino, apoyado clinicamente por la progresion del edema estromal desde la periferia.

Anti-vascular endothelial growth factor agents are frequently used to treat a variety of ocular neovascular diseases. While agents like bevacizumab and ranibizumab appear to be safe and effective, there have been reports of severe intraocular inflammation as well as sustained elevation of intraocular pressure (IOP) after single or multiple intravitreal injections of these protein-based therapeutics. The true mechanism leading to inflammation and/or sustained spikes in IOP remains unknown. We report a patient with sustained IOP elevation and kerato-precipitates on the trabecular meshwork after multiple injections of both bevacizumab and ranibizumab. We propose that monomer antibodies, aggregated proteins, or other high molecular weight molecules might lead to inflammation in the trabecular meshwork and subsequent elevation in IOP.

• A connatal and two adult cases of monosymptomatic endotheliitis plus trabeculitis could be correlated with culturable CMV or the presence of CMV DNA in the aqueous humor.

A patient had Fuchs heterochromic iridocyclitis of approximately 17 years' duration. Histologically, keratic precipitates, iris atrophy, rubeosis iridis, discontinuous rubeosis of the anterior chamber angle, a chronic nongranulomatous iridocyclitis, and trabeculitis were noted. The cause of the glaucoma probably is a combination of rubeosis of the anterior chamber angle and trabeculitis.

Diagnosis and treatment of herpes simplex virus eye diseases has benefitted from a vast amount of clinical and experimental studies. In this short presentation reference can only be made to some fields, which may illustrate--pars pro toto--the progress achieved during the last years. Clinico-virological correlation studies have led to a better understanding and classification of different typical clinical pictures, especially those affecting the structures of the anterior chamber: endotheliitis trabeculitis, and focal serous iritis. Antiherpetic drugs have become available which do not only penetrate the cornea in sufficient amounts but can also be used systemically. This will lead to a new role of steroids in the treatment of intraocular herpetic diseases. The combination of high-titer human interferon eye drops with a basic therapy of topical antiviral agents has considerably improved therapeutic results in dendritic keratitis.