The purpose of this review is to provide a comprehensive and updated overview of the clinical features, imaging modalities, differential diagnosis, diagnostic criteria, and treatment options for Vogt-Koyanagi-Harada (VKH) syndrome, a rare progressive inflammatory condition characterized by bilateral granulomatous panuveitis and systemic manifestations. While the clinical features and disease course of VKH syndrome are well-characterized in the literature, its diagnosis is challenging due to a broad differential that include infectious and noninfectious causes of uveitis and rare inflammatory conditions, as well as a lack of a single diagnostic finding on exam, laboratory testing, or imaging. The evolution of the diagnostic criteria for VKH syndrome reflects the growing understanding of the disease by the ophthalmic community and advancement of imaging technology. Findings on enhanced depth imaging (EDI) optical coherence tomography (OCT) and indocyanine green angiography (ICGA) help detect subtle inflammation of the choroid and were incorporated into new diagnostic criteria developed in the last few years. There is limited research on the treatment for acute VKH, but results of studies to date support the early initiation of immunomodulatory therapy (IMT) due to a high recurrence rate and progression to chronic disease in patients treated with monotherapy with high-dose systemic corticosteroids. This review will provide an in-depth summary of recent literature on advanced imaging modality and IMT to guide clinicians in their management of patients with VKH syndrome.

Background: A variety of experimental animal models are used in basic ophthalmological research to elucidate physiological mechanisms of vision and disease pathogenesis. The choice of animal model is based on the measurability of specific parameters or structures, the applicability of clinical measurement technologies, and the similarity to human eye function. Studies of eye pathology usually compare optical parameters between a healthy and altered state, so accurate baseline assessments are critical, but few reports have comprehensively examined the normal anatomical structures and physiological functions in these models.

Methods: Three cynomolgus monkeys, six New Zealand rabbits, ten Sprague Dawley (SD) rats, and BALB/c mice were examined by fundus photography (FP), fundus fluorescein angiography (FFA), and optical coherence tomography (OCT).

Results: Most retinal structures of cynomolgus monkey were anatomically similar to the corresponding human structures as revealed by FP, FFA, and OCT. New Zealand rabbits have large eyeballs, but they have large optic disc and myelinated retinal nerve fibers in their retinas, and the growth pattern of retinal vessels were also different to the human retinas. Unlike monkeys and rabbits, the retinal vessels of SD rats and BALB/c mice were widely distributed and clear. The OCT performance of them were similar with human beings except the macular.

Conclusions: Monkey is a good model to study changes in retinal structure associated with fundus disease, rabbits are not suitable for studies on retinal vessel diseases and optic nerve diseases, and rats and mice are good models for retinal vascular diseases. These measures will help guide the choice of model and measurement technology and reduce the number of experimental animals required.

Contrast is the differential luminance between one object and another. Contrast sensitivity (CS) quantifies the ability to detect this difference: estimating contrast threshold provides information about the quality of vision and helps diagnose and monitor eye diseases. High contrast visual acuity assessment is traditionally performed in the eye care practice, whereas the estimate of the discrimination of low contrast targets, an important complementary task for the perception of details, is far less employed. An example is driving when the contrast between vehicles, obstacles, pedestrians, and the background is reduced by fog. Many conditions can selectively degrade CS, while visual acuity remains intact. In addition to spatial CS, “temporal” CS is defined as the ability to discriminate luminance differences in the temporal domain, i.e., to discriminate information that reaches the visual cortex as a function of time. Likewise, temporal sensitivity of the visual system can be investigated in terms of critical fusion frequency (CFF), an indicator of the integrity of the magnocellular system that is responsible for the perception of transient stimulations. As a matter of fact, temporal resolution can be abnormal in neuro-ophthalmological clinical conditions. This paper aims at considering CS and its application to the clinical practice.

Abstract: Primary vitreoretinal lymphoma (PVRL), as a subset of primary central nervous system lymphoma (PCNSL), is a rare and fatal ocular malignancy. Most PVRL masquerades as chronic posterior uveitis, which makes the clinical diagnosis challenging. Vitreous cells, subretinal lesions and imaging techniques are essential for clinical diagnosis. Importantly, cytopathology/histopathology identification of malignant cells is the gold standard for the diagnosis of PVRL. In addition, molecular detection of immunoglobulin heavy chain (IgH) or T cell receptor (TCR) gene rearrangements, immunophenotyping for cell markers, and cytokine analysis of interleukine-10 elevation are often used as adjunct procedures. Current management of PVRL involves local radiation, intravitreal chemotherapy (methotrexate and rituximab), with or without systemic chemotherapy depending on the involvement of non-ocular tissues. In cases with concomitant PCNSL, systemic high-dose methotrexate/rituximab based therapy in conjunction with local therapy, whole brain radiotherapy and/or autologous stem cell transplantation is considered. Although PVRL normally responds well to initial treatment, high rates of relapse and CNS involvement usually lead to poor prognosis and limited survival. A professional team of medical experts in ophthalmologists, ocular pathologists, neuro-oncologists and hemato-oncologists is essential for optimizing patient management.

Background: To settle the fundamentals of a numerical procedure that relates retinal ganglion-cell density and threshold sensitivity in the visual field. The sensitivity of a generated retina and visual pathways to virtual stimuli are simulated, and the conditions required to reproduce glaucoma-type defects both in the optic-nerve head (ONH) and visual fields are explored.

Methods: A definition of selected structural elements of the optic pathways is a requisite to a translation of clinical knowledge to computer programs for visual field exploration. The program is able to generate a database of normalized visual fields. The relationship between the number of extant receptive fields and threshold sensitivity is plotted for background sensitivity and corresponding automated perimetry. A solution in two planes to the 3D distribution of axons in the ONH is proposed. Visual fields with induced damage in the optic disc are comparable in pattern and quantity to glaucomatous records.

Results: The two-level simulation of the ONH facilitates the analysis of optic-cup/retinal defects. We can generate the virtual optic pathways tailored to the age and morphology of the patient’s eye, and it is possible to reproduce glaucomatous damage by “reverse engineering” engineering. The virtual cortical model renders a quantitative relationship between visual defect and neural damage.

Conclusions: A two-level computing of the retina/optic nerve facilitates the analysis of neuroretinal defects and can be incorporated to automatic perimeters to facilitate visual field analysis.

Abstract: Encapsulated-cell therapy (ECT) is an attractive approach for continuously delivering freshly synthesized therapeutics to treat sight-threatening posterior eye diseases, circumventing repeated invasive intravitreal injections and improving local drug availability clinically. Composite collagen-alginate (CAC) scaffold in ECT contains an interpenetrating network that integrates the physical and biological merits of its constituents, including biocompatibility, mild gelling properties and availability. An injectable CAC system that supported the growth of HEK293 cells with sustainable glial-derived neurotrophic factor (GDNF) delivery has been developed. Continuous GDNF delivery was detected in culture and in healthy rat eyes for at least 14 days. The gels were well tolerated with no host tissue attachment and contained living cell colonies. Most importantly, gel implantation in dystrophic Royal College of Surgeons rat eyes for 28 days retained photoreceptors while those gels containing higher initial cell number yielded better photoreceptor rescue effect. This rescue effect is clinically relevant as photoreceptor death is a common pathology in many retinal diseases. Moreover, since cells including autologous cells can be genetically engineered to secrete various therapeutic agents, CAC gel offers a flexible system design and is a potential treatment option for other chronic neurodegenerative diseases.

Abstract: Blinding diseases such as photoreceptor degenerations are debilitating conditions that severely impair daily lives of affected patients. This group of diseases are amenable to photoreceptor replacement therapies and recent transplantation studies provided proof-of-principle for functional recovery at the retinal and behavioral level, though the actual mechanism of repair still needs further investigations. The immune system responds in several ways upon photoreceptor engraftment, resulting in T-cell and macrophage infiltrations and, consequently, decrease in graft survival. Most studies on the role of the immune system suggest a detrimental effect in a therapeutic setting. Conversely, the opposite idea wherein the immune system can be activated towards a protective state was also explored in other experimental paradigms. Here, Neves and colleagues explored the potential of cross-species studies and, to a certain extent, the concept of a protective immune system in retinal degeneration and therapy. Mesencephalic astrocyte-derived neurotrophic factor (MANF) was identified in this study as a novel factor that, by modulating the immune system, can slow down photoreceptor degeneration and improve transplantation outcome.

Abstract: Diabetic retinopathy (DR) is a complex multifactorial disease and one of the leading causes of visual impairment worldwide. DR pathogenesis is still not completely understood and, even if studies performed in the past focused on microvascular dysfunction as the main event, growing body of scientific evidence has demonstrated an important role of inflammation and neurodegeneration in the onset and progression of DR. This review summarizes current literature on the role of inflammation in the pathogenesis and progression of DR. In particular, it focuses on clinical inflammatory biomarkers detectable with non-invasive retinal imaging, suggestive of a local inflammatory condition. Current available treatments are applicable only at advanced stages of disease, therefore, there is the need to detect biomarkers of subclinical or early DR that can help in DR management before irreversible damage occurs. A better understanding of inflammatory pathways involved in DR may permit to implement more specific and personalized therapeutic strategies and clinical biomarkers may be a helpful tool in the everyday clinical practice to direct the patient to the most appropriate treatment option.