Search Results (35)

Background: Graft-versus-host disease (GvHD) is an overactive systemic inflammatory response that can arise following allogeneic hematopoietic stem cell transplantation (HSCT). This condition occurs when the transplanted donor immune cells recognize the recipient’s tissues as foreign and trigger an immune response against them. The ocular surface (eyelids, conjunctiva, meibomian glands, lacrimal glands, and cornea) is particularly involved in GvHD, and its response to existing treatments, including potent immunosuppressants and new targeted therapies, is undesirable, with such treatments often being ineffective. Human allogeneic umbilical cord blood platelet lysate stands out as a potent adjunct to conventional therapies for ocular surface disorders related to severe Dry Eye Disease. This study aimed to evaluate the safety and efficacy of umbilical cord blood platelet lysate eyedrops for the treatment of severe ocular surface disorders in graft-versus-host disease patients who have received previous unsuccessful treatments. Methods: This study was a prospective, non-comparative, interventional case series study involving 22 patients (10 females and 12 males) aged 25–46 years with severe ocular surface disorders that were unresponsive to standard treatments. The GvHD patients were categorized based on the severity of their ocular surface disorders into three groups: Group I: five patients with severe Dry Eye Disease and filamentary keratitis; Group II: eight patients suffering from severe blepharo-kerato-epitheliopathy; Group III: nine patients with corneal ulcers. Fresh umbilical cord blood (UCB) was obtained from healthy donors and subjected to centrifugation using a novel PRP preparation kit provided by Sciacca (AG) Cord blood bank, Italy in a one-step process. In all groups, the outcomes before and after treatment were evaluated by means of the OSDI (Ocular Surface Disease Index), SANDE (Symptom Assessment in Dry Eye) questionnaire, VAS (Visual Analogue Scale), slit lamp examination, Esthesiometry, Lissamine Green Staining, the NIBUT (Non-Invasive Break-Up Time) and BUT, fluorescein staining with digital photography and Oxford classification, the Schirmer Test, the Best Corrected Visual Acuity (BCVA), and Meibography. In Group III at each evaluation time, the size of the ulcer and its relative reduction compared to the baseline size were recorded. Clinical variables, such as corneal inflammation, conjunctivalization, corneal neovascularization, or pain, were also considered individually. Results: We observed a significant improvement in the SANDE, VAS, and OSDI scores; Schirmer Test; BUT; BCVA; and Oxford classification after treatment with allogeneic cord blood serum eyedrops. Nevertheless, pain and inflammation reduced markedly over time until complete healing in all cases. The mean reduction in the ulcer surface area (compared to baseline values) was significantly higher at all assessment points (p = 0.001 for day 7 and p < 0.001 for subsequent time points every 30 days for 90 days). At the last check-up (after 90 days of treatment), the number of ulcers (Group III, nine patients) with a reduction in size of greater than 50% was eight (88.8%), of which seven ulcers were completely healed. None of the patients experienced treatment-related local or systemic adverse events. In this study, using a relatively large number of cases, we demonstrated that the use of umbilical cord blood platelet lysate eyedrops is a safe, feasible, and effective curative approach for severe ocular surface disease in patients with GvHD. Conclusions: Our pilot study highlights the remarkable effectiveness of allogeneic cord blood serum eyedrops in patients with severe ocular surface disorders following GvHD who have shown an inadequate response to the usual treatments. It is mandatory to design future studies on the efficacy of this therapeutic approach for acute ocular, mucosal, and cutaneous GvHD. Full article

Objectives: To assess the clinical characteristics of patients with macular neovascularization (MNV) with no drusen in the fellow eye, we investigated the incidence of MNV in fellow eyes and the outcomes of intravitreal aflibercept (IVA) monotherapy in MNV eyes of patients with unilateral MNV with a punctate hyperfluorescence spot (PHS) in the fellow eye. Methods: We retrospectively studied 58 treatment-naïve patients with unilateral MNV with no drusen in the fellow eye. Patients were classified into a PHS group (n = 29) or no-PHS group (n = 29) based on the presence of PHS. We evaluated the incidence of MNV in the fellow eye, and the retreatment rate after initiation of three monthly aflibercept injections over one year. Results: Fellow eyes in the PHS group had a thicker choroid (p < 0.05) and higher prevalence of pachychoroid pigment epitheliopathy (PPE) (p < 0.001). MNV eyes in the PHS group had a thicker choroid (p = 0.09). The PHS group had a lower retreatment rate (p < 0.05) and required fewer injections (p < 0.05) than the no-PHS group. MNV developed in one eye in both the PHS and no-PHS groups, and both cases occurred in areas of hypofluorescence on indocyanine green angiography within the PPE area before the onset of MNV. Conclusions: The PHS group frequently exhibited pachychoroid disease characteristics and responded better to IVA monotherapy than the no-PHS group. These groups may represent distinct populations of patients with unilateral MNV with no drusen in the fellow eye. Full article

Diabetic retinopathy is a leading cause of visual morbidity worldwide. Fundus autofluorescence is a rapid, non-invasive imaging modality that has gained increased popularity in recent years in the multimodal evaluation of diabetic retinopathy and, in particular, of diabetic macular oedema. Acquired using either a fundus camera or the confocal scanning laser ophthalmoscope, short-wavelength and near-infrared autofluorescence are the most used techniques in diabetic retinopathy. In diabetic macular oedema, short-wavelength autofluorescence, in its cystoid pattern, is useful for detecting cystoid macular oedema. Increased spot hyperautofluorescence in short-wavelength and granular changes in near-infrared autofluorescence correlate well with other imaging findings, indicating photoreceptor and retinal pigment epithelium damage and being associated with decreased visual acuity. While also being a marker of oxidative stress, increased short-wavelength autofluorescence in the setting of diabetic macular oedema appears to be a prognostic factor for poor visual outcome, even after the resolution of the intraretinal fluid. Autofluorescence also helps in the assessment of diabetic retinal pigment epitheliopathy and choroidopathy. Fundus autofluorescence is an evolving technology that will assist in gaining further insight into the pathophysiology of diabetic retinopathy and allow for a more comprehensive evaluation of these patients. Full article

This review covers the utility of electrophysiological studies relevant to inflammatory diseases of the retina in conditions such as acute posterior multifocal placoid pigment epitheliopathy, acute zonal occult outer retinopathy, Adamantiades–Behçet disease, autoimmune retinopathy and neuro-retinopathy, birdshot chorioretinopathy, multiple evanescent white dot syndrome, and Vogt–Koyanagi–Harada disease. Electrophysiological studies can help with the diagnosis, prognostication, evaluation of treatment effects, and follow-up for these conditions. Full article

Diabetes mellitus (DM) is one of the most prevalent diseases globally, and its prevalence is rapidly increasing. Most patients with a long-term history of DM present with some degree of keratopathy (DK). Despite its high incidence, the underlying inflammatory mechanism of DK has not been elucidated yet. For further insights into the underlying immunopathologic processes, we utilized streptozotocin-induced mice to model type 1 DM (T1D) and B6.Cg-Lepob/J mice to model type 2 DM (T2D). We evaluated the animals for the development of clinical manifestations of DK. Four weeks post-induction, the total frequencies of corneal CD45⁺CD11b⁺Ly-6G⁻ myeloid cells, with enhanced gene and protein expression levels for the proinflammatory cytokines TNF-α and IL-1β, were higher in both T1D and T2D animals. Additionally, the frequencies of myeloid cells/mm² in the sub-basal neural plexus (SBNP) were significantly higher in T1D and T2D compared to non-diabetic mice. DK clinical manifestations were observed four weeks post-induction, including significantly lower tear production, corneal sensitivity, and epitheliopathy. Nerve density in the SBNP and intraepithelial terminal endings per 40x field were lower in both models compared to the normal controls. The findings of this study indicate that DM alters the immune quiescent state of the cornea during disease onset, which may be associated with the progressive development of the clinical manifestations of DK. Full article

In this study, the severity of eye pain (EP) and associated objective findings were evaluated in aqueous-deficient dry eye (ADDE) patients using PainVision^®, a quantitative pain-measuring device. This study involved 53 eyes of 53 ADDE patients (6 males and 47 females; mean age: 64.4 ± 13.4 [mean ± SD] years). Of those, 18 eyes of 18 patients underwent punctal occlusion, and EP and objective findings in those patients were evaluated before and after treatment. In all patients, the severity of EP as measured by PainVision^® was assessed using the Pain Degree (PD). The median PD for the 53 patients was 30.6 µA/µA (interquartile range, 16.9–93.2), and the nasal and central corneal staining score and the upper lid-wiper epitheliopathy score were significantly correlated with PD (R = 0.33, 0.33, and 0.28, respectively) (all: p < 0.05). Using the least squares method, the central corneal staining score most significantly affected PD. In the 18 cases that underwent punctal occlusion, PD was significantly reduced (median PD: 24.8 to 7.1 µA/µA; p < 0.0001). Using the least squares method, the central corneal staining score and tear meniscus radius were significantly more influential as factors contributing to PD before and after treatment, and central corneal epithelial damage was the factor most associated with ADDE-related EP. Full article

Fabry disease (FD) is a recessive monogenic disease linked to chromosome X due to more than two hundred mutations in the alfa-galactosidase A (GLA) gene. Modifications of the GLA gene may cause the progressive accumulation of globotriaosylceramide (Gb3) and its deacylated form, globotriasylsphingosine (lyso-Gb3), in lysosomes of several types of cells of the heart, kidneys, skin, eyes, peripheral and central nervous system (not clearly and fully demonstrated), and gut with different and pleiotropic clinical symptoms. Among the main symptoms are acroparesthesias and pain crisis (involving the peripheral nervous system), hypohidrosis, abdominal pain, gut motility abnormalities (involving the autonomic system), and finally, cerebrovascular ischemic events due to macrovascular involvement (TIA and stroke) and lacunar strokes and white matter abnormalities due to a small vessel disease (SVS). Gb3 lysosomal accumulation causes cytoplasmatic disruption and subsequent cell death. Additional consequences of Gb3 deposits are inflammatory processes, abnormalities of leukocyte function, and impaired trafficking of some types of immune cells, including lymphocytes, monocytes, CD8+ cells, B cells, and dendritic cells. The involvement of inflammation in AFD pathogenesis conflicts with the reported poor correlation between CRP levels as an inflammation marker and clinical scores such as the Mainz Severity Score Index (MSSI). Also, some authors have suggested an autoimmune reaction is involved in the disease’s pathogenetic mechanism after the α-galactosidase A deficiency. Some studies have reported a high degree of neuronal apoptosis inhibiting protein as a critical anti-apoptotic mediator in children with Fabry disease compared to healthy controls. Notably, this apoptotic upregulation did not change after treatment with enzymatic replacement therapy (ERT), with a further upregulation of the apoptosis-inducing factor after ERT started. Gb3-accumulation has been reported to increase the degree of oxidative stress indexes and the production of reactive oxygen species (ROS). Lipids and proteins have been reported as oxidized and not functioning. Thus, neurological complications are linked to different pathogenetic molecular mechanisms. Progressive accumulation of Gb3 represents a possible pathogenetic event of peripheral nerve involvement. In contrast, central nervous system participation in the clinical setting of cerebrovascular ischemic events seems to be due to the epitheliopathy of Anderson–Fabry disease with lacunar lesions and white matter hyperintensities (WMHs). In this review manuscript, we revised molecular mechanisms of peripheral and central neurological complications of Anderson–Fabry Disease. The management of Fabry disease may be improved by the identification of biomarkers that reflect the clinical course, severity, and progression of the disease. Intensive research on biomarkers has been conducted over the years to detect novel markers that may potentially be used in clinical practice as a screening tool, in the context of the diagnostic process and as an indicator of response to treatment. Recent proteomic or metabolomic studies are in progress, investigating plasma proteome profiles in Fabry patients: these assessments may be useful to characterize the molecular pathology of the disease, improve the diagnostic process, and monitor the response to treatment. Full article

Punctal occlusion (PO) is considered to improve both tear-film instability and increased friction during blinking and may consequently affect blinks. The purpose of this study was to investigate the effect of PO on blinks. This study involved 16 eyes of 16 severe aqueous deficient dry eye (ADDE) patients (mean age: 65.7 years). In all eyes, tear meniscus radius (TMR), spread grade (SG) of the tear-film lipid layer (i.e., SG 1-5: 1 being the best), fluorescein break-up time (FBUT), corneal epithelial damage score (CED), conjunctival epithelial damage score, corneal filament (CF) grade, lid-wiper epitheliopathy (LWE) grade, and superior limbic keratoconjunctivitis (SLK) grade were evaluated at before and at more than 1-month after PO. Moreover, using a custom-made high-speed blink analyzer, palpebral aperture height, blink rate, upper-eyelid closing-phase amplitude/duration/maximum velocity, and upper-eyelid opening-phase amplitude/duration/maximum velocity were measured at the same time point. After PO, TMR, SG, FBUT, CED, and the CF, LWE, and SLK grades were significantly improved, and upper-eyelid opening/closing-phase amplitude and maximum velocity significantly increased (all p < 0.04). The findings of this study suggest that PO improves ocular surface lubrication and that blink-related parameters can reflect the friction that occurs during blinking in eyes with severe ADDE. Full article

Background: Dry eye disease is a significant disease in Singapore. While there have been studies using allogenic cord serum for the treatment of dry eye disease, treatment of dry eyes with allogenic umbilical cord plasma drops has yet to be started in Singapore. Purpose: To evaluate the effectiveness of umbilical cord plasma eyedrops for the treatment of recalcitrant dry eyes in a local Singaporean context. Methods: This is an observational, longitudinal, interventional study for dry eye patients who did not show clear improvement after standard therapy. Patients were recruited from 2020 to 2023 from the dry eye clinic of the Singapore National Eye Center. Umbilical cord plasma was delivered frozen to patients and stored in home freezers. All participants underwent a standardized clinical evaluation for dry eye, and data were collected. Results: There were 40 participants (7 males and 33 females). The duration of follow-up was 5.52 ± 1.57 months. Kerato-epitheliopathy staining score, TBUT (tear breakup time), and SPEED (Standard Patient Evaluation of Eye Dryness Questionnaire) scores significantly improved after treatment. No statistically significant improvement was found in terms of visual acuity, according to Schirmer’s score. Conclusion: Cord plasma eye drops significantly improved kerato-epitheliopathy staining scores in recalcitrant dry eye patients. Allogeneic plasma is a promising form of treatment for recalcitrant dry eye. Full article

The association between vaccines and ocular disorders has attracted significant attention in scientific research. Numerous mainstream vaccines are associated with a range of uveitis types, including anterior, intermediate, and posterior uveitis. Additionally, they are associated with distinct ocular diseases such as multifocal choroiditis, Vogt–Koyanagi–Harada (VKH) disease, acute posterior multifocal placoid pigment epitheliopathy (APMPPE), and multiple evanescent white dot syndrome (MEWDS). These ocular conditions are often transient, with a vast majority of patients experiencing improvement after steroid intervention. To date, numerous cases of vaccine-induced uveitis have been reported. This study analyzed the correlation between antiviral vaccines, including the hepatitis B virus (HBV), human papillomavirus (HPV), measles–mumps–rubella (MMR), varicella zoster virus (VZV), and influenza vaccines, and different manifestations of uveitis. This is the first comprehensive study to offer a detailed analysis of uveitis types induced by antiviral vaccines. Through an extensive database search, we found a particularly strong link between influenza vaccines, followed by VZV and HPV vaccines. While anterior uveitis is common, conditions such as APMPPE, MEWDS, and VKH are particularly notable and merit careful consideration in clinical practice. Corticosteroid treatment was effective; however, half of the observed patients did not achieve full recovery, indicating potentially prolonged effects of the vaccine. Full article

Our purpose is to describe blue-light fundus autofluorescence (BAF) features of inflammatory diseases of the outer retina characterised by photoreceptor damage. BAF from patients diagnosed with secondary and primary inflammatory photoreceptor damage were retrospectively analyzed and compared to other imaging modalities including fluorescein angiography (FA), indocyanine green angiography (ICGA), and spectral domain optical coherence tomography (SD-OCT). Multiple evanescent white dot syndrome (MEWDS), idiopathic multifocal choroiditis (MFC), acute posterior multifocal placoid pigment epitheliopathy (APMPPE), serpiginous choroiditis (SC), and acute syphilitic posterior placoid chorioretinitis (ASPPC), all cases corresponding to secondary photoreceptor diseases caused by inflammatory choriocapillaris nonperfusion, were included and compared to primary photoreceptor disease entities, including acute zonal occult outer retinopathy (AZOOR) and cancer-associated retinopathy (CAR). Both groups showed increased BAFs of variable intensity. In severe cases of APMPPE and ASPPC, BAF also showed hypoautofluorescent areas. In group 1 (secondary diseases) BAF hyperautofluorescent areas were associated with colocalized ICGA hypofluorescent areas, indicating choriocapillaris nonperfusion; whereas in group 2 (primary diseases), no ICGA signs were detected. The associated colocalized areas of hypofluorescence on ICGA in the first group, which were absent in the second group, were crucial to allow the differentiation between primary (photoreceptoritis) and secondary (choriocapillaritis) photoreceptor diseases. BAF patterns in inflammatory diseases of the outer retina can give relevant information on the photoreceptor and RPE involvement, with ICGA being crucial to detect concurring choriocapillaris damage and differentiating the two pathologies. Full article

Background: Optical coherence tomography angiography (OCTA) is a noninvasive imaging modality used to analyze the retinochoroidal vasculature and detect vascular flow. The resulting images can be segmented to view each vascular plexus individually. While fluorescein angiography is still the gold standard for the diagnosis of posterior uveitis, it has limitations, and can be replaced by OCTA in some cases. Methods: This case series describes five patients with posterior noninfectious uveitis and their description by OCTA. Results: Cases included lupus retinopathy (n = 1) for which OCTA showed ischemic maculopathy as areas of flow deficit at the superficial and deep capillary plexus; choroidal granulomas (n = 1) with a non-detectable flow signal in the choroid; active punctate inner choroiditis and multifocal choroiditis (n = 1) with OCTA that showed active inflammatory chorioretinal lesions as non-detectable flow signals in choriocapillaris and choroid; dense type 2 inflammatory secondary neovascularization (n = 1) associated with active choroiditis; and acute posterior multifocal placoid pigment epitheliopathy (APMPPE) (n = 1) without flow abnormalities at the superficial and deep retinal plexuses but non-detectable flow at the levels of the choriocapillaris and choroid. Conclusions: Ophthalmologists can use OCTA to identify inflammatory changes in retinal and choroidal vasculature, aiding in the diagnosis, management, and monitoring of posterior uveitis. Full article

Soft contact lens (SCL) perturbs the intimate connection between the pre-lens tear film (PLTF) and the ocular surface in various ways, i.e., (i) decrease in tear meniscus radius and aqueous tear thickness, (ii) attenuation of tear film lipid layer spread, (iii) limited wettability of SCL surface, (iv) increased friction with eyelid wiper, etc. This often results in SCL-related dry eye (SCLRDE) manifested as PLTF instability and contact lens discomfort (CLD). In this review, the individual contributions of factors (i–iv) to PLTF breakup patterns (BUP) and CLD are considered via the tear film-oriented diagnosis framework adopted by the Asia Dry Eye Society from a clinical and basic science perspective. It is shown that SCLRDE (due to aqueous deficiency, increased evaporation, or decreased wettability) and BUP of PLTF classify within the same types as the ones observed for the precorneal tear film. The analysis of PLTF dynamics reveals that the inclusion of SCL enhances the manifestation of BUP associated with (i) decreased thickness of PLTF aqueous layer and (ii) limited SCL wettability as shown by the rapid expansion of BUP area. PLTF thinness and instability result in increased blink-related friction and lid wiper epitheliopathy as major contributor to CLD. Full article

Epitheliopathy at the ocular surface is a defining sign of dry eye disease, a common disorder that affects 10% to 30% of the world’s population. Hyperosmolarity of the tear film is one of the main drivers of pathology, with subsequent endoplasmic reticulum (ER) stress, the resulting unfolded protein response (UPR), and caspase-3 activation implicated in the pathway to programmed cell death. Dynasore, is a small molecule inhibitor of dynamin GTPases that has shown therapeutic effects in a variety of disease models involving oxidative stress. Recently we showed that dynasore protects corneal epithelial cells exposed to the oxidant tBHP, by selective reduction in expression of CHOP, a marker of the UPR PERK branch. Here we investigated the capacity of dynasore to protect corneal epithelial cells subjected to hyperosmotic stress (HOS). Similar to dynasore’s capacity to protect against tBHP exposure, dynasore inhibits the cell death pathway triggered by HOS, protecting against ER stress and maintaining a homeostatic level of UPR activity. However, unlike with tBHP exposure, UPR activation due to HOS is independent of PERK and mostly driven by the UPR IRE1 branch. Our results demonstrate the role of the UPR in HOS-driven damage, and the potential of dynasore as a treatment to prevent dry eye epitheliopathy. Full article

Background: The global and precise follow-up of uveitis has become possible with the availability of dual fluorescein (FA) and indocyanine green angiography (ICGA) since the mid-1990s. Progressively, additional non-invasive imaging methods have emerged, bringing value-added precision to the imaging appraisal of uveitis, including, among others, optical coherence tomography (OCT), enhanced-depth imaging OCT (EDI-OCT) and blue light fundus autofluorescence (BAF). More recently, another complementary imaging method, OCT-angiography (OCT-A), further allowed retinal and choroidal circulation to be imaged without the need for dye injection. Purpose: The purpose of this review was aimed at examining the evidence in published reports indicating whether OCT-A could possibly replace dye angiographic methods, as well as the real practical impact of OCT-A. Methods: A literature search in the PubMed database was performed using the terms OCT-angiography and uveitis, OCTA and uveitis and OCT-A and uveitis. Case reports were excluded. Articles were classified into technical reports, research reports and reviews. Articles in the two latter categories were analyzed in a more detailed, individual fashion. Special attention was paid to whether there were arguments in favor of an exclusive rather than complementary use of OCT-A. Furthermore, a synthesis of the main practical applications of OCT-A in the management of uveitis was attempted. Results: Between 2016 (the year of the first articles) and 2022, 144 articles containing the search terms were identified. After excluding case report articles, 114 articles were retained: 4 in 2016, 17 in 2017, 14 in 2018, 21 in 2019, 14 in 2020, 18 in 2021 and 26 in 2022. Seven articles contained technical information or consensus-based terminology. Ninety-two articles could be considered as clinical research articles. Of those, only two hinted in their conclusions that OCT-A could hypothetically replace dye methods. The terms mostly used to qualify the contribution of the articles in this group were “complementary to dye methods”, “adjunct”, “supplementing” and other similar terms. Fifteen articles were reviews, none of which hinted that OCT-A could replace dye methods. The situations where OCT-A represented a significant practical contribution to the practical appraisal of uveitis were identified. Conclusion: To date, no evidence was found in the literature that OCT-A can replace the classic dye methods; however, it can complement them. Promoting the possibility that non-invasive OCT-A can substitute the invasive dye methods is deleterious, giving the elusive impression that dye methods are no longer inevitable for evaluating uveitis patients. Nevertheless, OCT-A is a precious tool in uveitis research. Full article