Editorial on Uveitis and Intraocular Inflammations

Uveitides are complex intraocular inflammatory disorders of diverse causes and variable clinical course that are complicated by vision threatening sequelae. Besides common bacterial or viral causes of infectious uveitis, inflammation of ocular coats ranging from noninfective scleritis, parasitic conditions like intraocular toxoplasmosis to the severe globe threatening conditions like aspergillus endophthalmitis, the uveitides spectrum has been frequently reported in the Asia-Pacific region and beyond.1–3 The enigma of uveitides is slowly getting decoded by a spectrum of parallel works like activation of the interleukin-23/interleukin-17 signalling pathway in autoimmune conditions, and reviews on commoner conditions like Fuchs uveitis syndrome to management trials published by the FAST research group.4–6 The majority of uveitides are initiated and perpetuated by infectious agents: viruses, bacteria, fungi, and parasites. In the Asia-Pacific region, the infectious uveitides are important causes of blindness as a result of chronic inflammation and inflicting damage to the retina and other intraocular structures. Incidence and prevalence of the uveitides vary and depend on geography, endemic nature, and epidemics of infectious diseases. Intraocular tuberculosis and leprosy are endemic in several Asia-Pacific countries.7 This region is prone to periodic resurgences of infections such as dengue, West Nile virus, chikungunya virus, leptospirosis, trematodes, and nematodes. Globally, prevalent infectious uveitides include ocular toxoplasmosis, syphilis, and herpetic infections. Akhter and Toy8 address limitations in knowing the prevalence and incidence of various uveitides and discuss advantages of using a big database to reveal geographic distribution and demographic features of various infectious uveitides. Their group used nationwide medical claims databases to estimate incidence and prevalence of infectious uveitis in the United States. This showed that the prevalence and incidences of infectious uveitis were higher than previously reported. There are challenges in arriving at a diagnosis of the infectious uveitides, as several of the uveitides present virtually similar clinical findings.7 Moreover, a single infectious agent can present with diverse clinical features. Thus, the infectious uveitides require epidemiologic consideration, tailored systemic laboratory investigations, and imaging like x-ray of chest and other organs, ocular fluid examination, and imaging of intraocular structures. Current ocular imaging techniques, fluorescein and indocyanine green angiography, fundus autofluorescence, optical coherence tomography, and optical coherence tomography angiography are found helpful in the diagnosis of the intraocular infections, presenting with clinical features of posterior and panuveitis, and monitoring response to antimicrobial and other interventions. These imaging modalities are also helpful in the diagnosis of tissue damage, adjusting levels of therapeutic agents and detection of complications such as cystoid macular edema, epiretinal membrane formation, and choroidal neovascularization. Padmamalini et al9 showed importance of multimodal ocular imaging in delineating various infectious and noninfectious uveitides and recommended their use in the diagnosis and management of the uveitides and retinal vasculitis. In the past, diagnosis of infectious uveitis required culturing of and/or microscopic detection of infectious agents from ocular tissue, sputum, blood cultures, or ocular fluid samples. These approaches are suboptimal in detection of the microbes due to their low sensitivity. Introduction of molecular techniques, such as direct polymerase chain reaction (PCR), multiplex PCR, targeted universal multiplex PCR, and targeted sequencing of 16S rRNA for bacterial detection advanced the field of infectious uveitides by virtue of high sensitivity in detection of a causative agent. Unlike the culturing of infectious agents, these molecular techniques are rapid in detecting the infectious agents and serve to confirm or support clinical diagnosis of infectious uveitides. Drawbacks of these techniques are low specificity, false positives, and false negative results. Furthermore, these techniques cannot detect unknown infectious agents when required primers for such microbe(s) are unavailable. A novel molecular technique, metagenomic next-generation sequencing (mNGS), appears to address the detection of hitherto undiscovered infectious agent causing uveitis.10 This sequencing has gained importance in diagnosis of unexpected and undiscovered organisms and known infectious agents. This technique combined with bioinformatics could prove to be a highly sensitive and rapid technique in the etiologic diagnosis of infectious uveitides utilizing intraocular fluid or tissue biopsy samples. Moreover, this technique is unbiased and can provide quantification of the infectious agents. Such unbiased detection of unknown infectious agents could become a major approach in the diagnosis of infectious uveitides. However, wide clinical adaptation of mNGS may take time. In uveitis, significant cause of vision loss derives from macular edema requiring proper intervention with anti-inflammatory agents delivered either locally or by systemic route. Sheu et al11 provide various options and indications for the local delivery of corticosteroids, immunosuppressive and biological agents in noninfectious uveitides. Several systemically delivered biological agents are successfully employed in the treatment of recalcitrant noninfectious uveitides. Vitreoretinal large B-cell lymphoma is a well-known masquerade of infectious and noninfectious posterior or panuveitis. In their review, Takhar et al12 emphasize the importance of the lymphoma's diagnosis utilizing modern techniques in detection of a lymphoma-associated mutation in the myeloid differentiation primary response gene 88 (MYD 88). The metagenomic deep sequencing as used in detection of infectious agent(s) is also found useful in identifying MYD 88 mutations in vitreoretinal lymphomas. This technique could offer several advantages in diagnosis of the lymphoma with a small volume of intraocular fluid. In conclusion, infectious uveitides are treatable by timely mitigation with early etiologic diagnosis, timely administration of antimicrobials, and judicious use of anti-inflammatory agents, either through systemic or local administration. However, proper diagnosis requires ocular and other imaging and laboratory support. The utilization of molecular approaches has paved a way for early detection of infectious agents. The recent introduction of mNGS could revolutionize rapid detection of unknown infectious agents in uveitides. This technique combined with bioinformatics could advance the field of diagnosis and management of intraocular infections and vitreoretinal lymphomas.