Diagnostic and therapeutic considerations in patients with bilateral diffuse uveal melanocytic proliferation.

PURPOSE: This review aims to summarize the current knowledge concerning the clinical features, diagnostic work-up, and therapeutic approach of bilateral diffuse uveal melanocytic proliferation (BDUMP). METHODS: A meticulous literature search was performed in the PubMed database. A supplementary search was made in Google Scholar to complete the collected items. Our search strategy utilized the following keywords: "bilateral diffuse uveal melanocytic proliferation", "BDUMP", and "Paraneoplastic Syndrome". Articles were considered based on their relevance, with the search spanning publications up to 2023. Studies were excluded if they did not contribute pertinent information or lacked methodological rigor. A critical appraisal of included studies was conducted, assessing study design, sample size, methodology, and potential bias, ensuring a thorough and transparent review process. RESULTS: BDUMP is a rare and potentially sight-threatening condition characterized by the bilateral proliferation of melanocytes within the uvea. BDUMP is typically observed in middle-aged or elderly individuals and is often associated with an underlying malignancy, most commonly of gastrointestinal origin. BDUMP is frequently misdiagnosed as a benign nevus or choroidal metastasis, leading to delayed diagnosis and treatment. The ophthalmic symptoms and signs typically precede the diagnosis of a systemic malignancy, emphasizing the crucial role of ophthalmologists in the recognition of BDUMP. Several diagnostic modalities can aid in the diagnosis of BDUMP, including ophthalmic examination, imaging studies such as optical coherence tomography, fluorescein angiography, and indocyanine green angiography, and biopsy of the uveal tissue. Treatment of BDUMP is directed towards the underlying malignancy and may include chemotherapy, radiotherapy, or surgical resection. Additionally, strict monitoring with regular follow-ups may contribute to the detection of new lesions and the reduction in the size of existing ones. CONCLUSIONS: BDUMP can be considered a potential biomarker in the management of malignancies, especially when the primary underlying tumor has not been detected. Further research is needed to better understand the pathogenesis of BDUMP and its association with malignancy.

Diagnostic and therapeutic challenges in acute retinal necrosis; an update.

Acute retinal necrosis (ARN) is a rare but severe ophthalmic pathology defined by panuveitis, retinal necrosis, and high rates of retinal detachment. ARN may lead to poor visual outcomes even if promptly diagnosed and treated. ARN may present with a wide spectrum of clinical findings compatible with panuveitis including anterior uveitis, scleritis, vitritis, necrotizing retinitis, occlusive vasculitis, and optic disc edema. The American Uveitis Society introduced clinical criteria in 1994 for the diagnosis of ARN, while more recent criteria have been proposed by the Standardization of Uveitis Nomenclature (SUN) Working Group and the Japanese ARN Study Group. Multimodal imaging is a valuable tool in evaluating patients with ARN, particularly in unusual cases, while utilizing retinal imaging and applying AI algorithms in these areas of clinical research could be highly beneficial. Over the last few years, significant progress has been made in achieving timely diagnosis and treatment. The precise identification of the viral cause in suspected ARN cases has been greatly enhanced by the advancements in PCR techniques and flow cytometry used for intraocular fluids. systemic (intravenous or oral) antivirals with adjunctive intravitreal antiviral therapy are recommended as first-line therapy to reduce disease severity, the risk of vision loss, and retinal detachment incidence. Although aciclovir was the first existing antiviral agent, at present many clinicians prefer high-dose valaciclovir orally or intravenous aciclovir combined with intravitreal foscarnet. Despite significant progress in diagnosing and treating ARN, further research is needed to improve visual outcomes in this challenging clinical condition.

Punctate inner choroidopathy: A review of the current diagnostic and therapeutic approaches.

Punctate inner choroidopathy (PIC) is an uncommon idiopathic inflammatory condition characterized by multifocal chorioretinopathy that primarily affects young adults, with a predilection for myopic females. Clinically, it manifests as small, yellowish-white lesions in the inner choroid and outer retina, often associated with inflammatory changes. Accurate diagnosis remains a challenge due to its resemblance to other posterior uveitic entities, necessitating an astute clinical eye and advanced imaging techniques for differentiation. Multimodal imaging plays a crucial role by offering valuable insights, as it enables the visualization of various abnormalities related to uveitis. The pathogenesis of PIC is still a subject of debate, with a complex interplay of genetic, immunological, and environmental factors proposed. Managing PIC presents multiple challenges for clinicians. Firstly, variable disease severity within and among patients requires diverse treatments, from observation to aggressive immunosuppression and/or anti-VEGF therapy. Secondly, treatment must distinguish between primary causes of vision loss. New or worsening PIC lesions suggest active inflammation, while new neovascular membranes may indicate secondary neovascular processes. Thirdly, deciding on maintenance therapy is complex, balancing PIC prognosis variability against immunosuppression risks. Some patients have long periods of inactivity and remission, while others face sudden, vision-threatening episodes during quiescent phases. Through a systematic review of the literature, this paper sheds light on the current understanding of PIC, its challenges, and the prospects for future research. By synthesizing existing knowledge, it aims to aid clinicians in accurate diagnosis and guide treatment decisions for improved visual outcomes in individuals affected by PIC.

Central macular choriocapillaris impairment as a manifestation of microvascular disease in eyes with subretinal drusenoid deposits.

BACKGROUND/OBJECTIVES: Microvascular alterations and choroidal impairment are emerging as a pathologic pathway in age-related macular degeneration (AMD). This study aimed to evaluate the central macular choriocapillaris (CC) in eyes with subretinal drusenoid deposits (SDD) and the retinal microvasculature in patients with early AMD phenotypes. SUBJECTS/METHODS: This was an institutional, multicentric observational cross-sectional study. Ninety-nine eyes of 99 subjects; 33 eyes with SDD only, 33 eyes with conventional drusen (CD) only, and 33 eyes of healthy age-matched subjects were included. Comprehensive ophthalmologic examination and optical coherence tomography angiography (OCTA) was performed. The central macular flow area of the CC was analysed in the SDD group and the vessel density of the retinal superficial capillary plexus (SCP) and deep capillary plexus (DCP) was analysed in the SDD and CD groups using automated OCTA output parameters. RESULTS: The flow area of the CC in the SDD group was significantly reduced (p ≤ 0.001) with respect to the healthy control group. There was a trend of reduction of vessel density of the SCP and the DCP in the SDD and CD group with respect to controls, although this did not reach statistical significance. CONCLUSIONS: OCTA data in the present report corroborate the role of vascular damage in early AMD with CC impairment in the central macular area in eyes with SDD.

Subretinal drusenoid deposits as a biomarker of age-related macular degeneration progression via reduction of the choroidal vascularity index.

BACKGROUND/OBJECTIVES: This study aimed to analyse the role of the choroid in early age-related macular degeneration (AMD) by analysing choroidal vascularity index (CVI) in pure cohorts of patients with subretinal drusenoid deposits (SDD) or conventional drusen (CD). SUBJECTS/METHODS: This was an observational cross-sectional study. Comprehensive ophthalmologic examination and multimodal imaging including fundus photography, autofluorescence, near infrared reflectance, and spectral domain optical coherence tomography (SDOCT) was performed. CVI processing was performed on a foveal horizontal SDOCT scan with binarization using Image J Image software and calculated as the ratio between luminal area (LA) and total area (TA). RESULTS: Sixty-nine eyes of 69 participants were included; 23 eyes with SDD alone, 22 eyes with CD alone, and 24 control eyes of healthy age-matched subjects. CVI was significantly reduced in the SDD and CD group compared to controls (p = 0.0001). Post-hoc analysis revealed a significant reduction of CVI in the SDD versus the control group (p = 0.0002), in the CD versus the control group (p = 0.001), and in the SDD versus the CD group (p = 0.006). Covariance analysis showed a significant difference of LA (p = 0.033) but no significant difference of TA (p = 0.106) between the three groups. Direct comparison between CD and SDD showed a significant reduction of LA and TA in the SDD group. CONCLUSIONS: CVI may have prognostic implications in early AMD. SDD is a biomarker of AMD progression and the mechanism for this could be via reduction of the CVI.

Choroidal vascularity index and choroidal thickness: potential biomarkers in retinitis pigmentosa.

Retinitis pigmentosa (RP) is the commonest inherited retinal dystrophy. It is characterized by progressive photoreceptor degeneration and cell death and ongoing neuronal and vascular impairment. In recent years, pathophysiological alterations of the choroid have begun to be appreciated in RP. Thus, representing a potential diagnostic and therapeutic biomarker. In particular, choroidal thickness and the choroidal vascularity index can be used to understand the pathogenesis of disease and evaluate new therapeutic possibilities. Photoreceptor changes seen in eyes with RP are directly correlated to a decrease of choroidal flow, leading to a strong association between relative choroidal ischemia and visual impairment. In this review we analyse the literature on choroidal thickness and choroidal vascularity index in patients with RP and assess whether these markers may reflect progression of disease from an anatomical and functional point of view.

The Role of the Choroid in Stargardt Disease.

Stargardt disease is the commonest juvenile macular dystrophy. It is caused by genetic mutations in the ABCA4 gene. Diagnosis is not always straightforward, and various phenocopies exist. Late-onset disease can be misdiagnosed with age-related macular disease. A correct diagnosis is particularly critical because of emergent gene therapies. Stargardt disease is known to affect retinal pigment epithelium and photoreceptors. Many studies have also highlighted the importance of the choroid in the diagnosis, pathophysiology, and progression of the disease. The choroid is in an integral relationship with the retinal pigment epithelium and photoreceptors, and its possible involvement during the disease should be considered. The purpose of this review is to analyze the current diagnostic tools for choroidal evaluation and the extrapolation of useful data for ophthalmologists and researchers studying the disease.

Age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the developed world. Despite recent advances in treatment, AMD causes considerable morbidity. For the non-ophthalmologist, a brief background on retinal structure is provided, followed by a description of the characteristic changes seen in AMD. Subsequently the typical clinical features of AMD are discussed with an outline of present management, followed by the current theories of AMD pathogenesis. The similarities between AMD and another neurodegenerative disease are then highlighted. Finally, we review the on-going clinical trials of potential treatments for the future. Since it is clear that multiple risk factors are involved in the pathogenesis of AMD, a multi-faceted approach will most likely be required in order to prevent further patients progressing to blindness as a result of this devastating condition.

Fine mapping of the X-linked recessive congenital idiopathic nystagmus locus at Xq24-q26.3.

PURPOSE: To refine the interval for X-linked congenital idiopathic nystagmus at Xq24-q26.3 and to evaluate a novel candidate gene (Muscleblind-like 3 gene [MBNL3]). METHODS: A single pedigree with congenital idiopathic nystagmus (CIN) inherited as an X-linked recessive trait underwent detailed clinical examination including nystagmology and electrophysiological investigation in selected subjects. Following detailed phenotyping, genotyping was performed using 52 microsatellite markers spaced at an average of 5 cM along the X chromosome. Subsequent two-point and multipoint linkage analysis were performed and a candidate gene was screened for mutations by conventional sequencing. RESULTS: Linkage mapping located the disease gene to a 15.5cM interval at Xq24-q26.3, between markers DXS1212 and DXS1062 with a maximum two-point LOD score of 4.24 with both markers DXS8044 and DXS994 (theta=0). Multipoint analysis indicated a LOD score of 4.54 and a critical gene interval of 8.0 cM. No mutations were found in the MBNL3 gene in this pedigree. CONCLUSIONS: We describe a family with an unusual inheritance pattern most consistent with X-linked recessive inheritance with X inactivation causing manifesting females. We refine the linkage interval for X-linked recessive congenital idiopathic nystagmus and exclude MBNL3 as the causative gene in this family.