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Anterior and posterior segment changes in rat eyes with chronic steroid administration and their responsiveness to antiglaucoma drugs

Razali N, Agarwal R, Agarwal P, Kapitonova MY, Kannan Kutty M, Smirnov A, et al.

Eur J Pharmacol, 2015 Feb 15;749:73-80.
PMID: 25481859 DOI: 10.1016/j.ejphar.2014.11.029

Steroid-induced ocular hypertension (SIOH) is associated with topical and systemic use of steroids. However, SIOH-associated anterior and posterior segment morphological changes in rats have not been described widely. Here we describe the pattern of intraocular pressure (IOP) changes, quantitative assessment of trabecular meshwork (TM) and retinal morphological changes and changes in retinal redox status in response to chronic dexamethasone treatment in rats. We also evaluated the responsiveness of steroid-pretreated rat eyes to 5 different classes of antiglaucoma drugs that act by different mechanisms. Up to 80% of dexamethasone treated animals achieved significant and sustained IOP elevation. TM thickness was significantly increased and number of TM cells was significantly reduced in SIOH rats compared to the vehicle-treated rats. Quantitative assessment of retinal morphology showed significantly reduced thickness of ganglion cell layer (GCL) and inner retina (IR) in SIOH rats compared to vehicle-treated rats. Estimation of retinal antioxidants including catalase, superoxide dismutase and glutathione showed significantly increased retinal oxidative stress in SIOH animals. Furthermore, steroid-treated eyes showed significant IOP lowering in response to treatment with 5 different drug classes. This indicated the ability of SIOH eyes to respond to drugs acting by different mechanisms. In conclusion, SIOH was associated with significant morphological changes in TM and retina and retinal redox status. Additionally, SIOH eyes also showed IOP lowering in response to drugs that act by different mechanisms of action. Hence, SIOH rats appear to be an inexpensive and noninvasive model for studying the experimental antiglaucoma drugs for IOP lowering and neuroprotective effects.

Matched MeSH terms: Retina/pathology
Baseline retinal nerve fiber layer thickness as a predictor of multiple sclerosis progression: New insights from the FREEDOMS II study

Wang L, Tan H, Yu J, ZhangBao J, Huang W, Chang X, et al.

Eur J Neurol, 2023 Feb;30(2):443-452.
PMID: 36286605 DOI: 10.1111/ene.15612

BACKGROUND AND PURPOSE: The aim was to evaluate the potential of retinal nerve fiber layer thickness (RNFLT) measured with optical coherence tomography in predicting disease progression in relapsing-remitting multiple sclerosis (RRMS).
METHODS: Analyses were conducted post hoc of this 24-month, phase III, double-blind study, in which RRMS patients were randomized (1:1:1) to once daily oral fingolimod 0.5 mg, 1.25 mg or placebo. The key outcomes were the association between baseline RNFLT and baseline clinical characteristics and clinical/imaging outcomes up to 24 months. Change of RNFLT with fingolimod versus placebo within 24 months and time to retinal nerve fiber layer (RNFL) thinning were evaluated.
RESULTS: Altogether 885 patients were included. At baseline, lower RNFLT was correlated with higher Expanded Disability Status Scale score (r = -1.085, p = 0.018), lower brain volume (r = 0.025, p = 0.006) and deep gray matter volume (r = 0.731, p

Matched MeSH terms: Retina/pathology
Early effect of hydroxychloroquine therapy: relationship between cumulative dose and retinal thickness

Agarwal P, Wong YH, Das Gupta E, Agarwal R, Livingstone BI, Ramamurthy S, et al.

Cutan Ocul Toxicol, 2015;34(3):179-84.
PMID: 25068998 DOI: 10.3109/15569527.2014.938751

BACKGROUND: Hydroxychloroquine (HCQ) is widely used for long-term treatment of autoimmune diseases such as rheumatoid arthritis. However, its long-term use is known to be associated with visual changes due to retinal damage. Retinal damage associated with long-term HCQ therapy is preventable if the drug is discontinued early when the patients are still asymptomatic. In view of contrasting reports from previous studies, we investigated the association of prolonged HCQ therapy with retinal thickness in macular area.
METHODS: This study included 48 patients on long-term HCQ therapy and 38 healthy controls. All subjects underwent examination for corrected visual acuity, fundus photography, visual fields and SD-OCT for retinal thickness.
RESULTS: Visual acuity, visual fields, fundus photography and SD-OCT did not reveal changes consistent with diagnosis of established HCQ retinopathy in any of the subjects from HCQ group. Retinal thickness in central, parafoveal and perifoveal areas did not show significant differences between HCQ and control groups. However, we observed negative correlation between cumulative dose and retinal thickness in the parafoveal (p = 0.003) and perifoveal areas (p = 0.019) but not in the central area.
CONCLUSIONS: Correlation of cumulative dose with retinal thickness in parafoveal and perifoveal areas and not the central area is in accordance with the late appearance of HCQ-induced bull's eye retinopathy. Hence screening of asymptomatic patients using OCT seems to be of great importance for early detection of retinal changes.
KEYWORDS: Cumulative dose; OCT; hydroxychloroquine; retinal thickness

Matched MeSH terms: Retina/pathology
Vascular intersection detection in retina fundus images using a new hybrid approach

Aibinu AM, Iqbal MI, Shafie AA, Salami MJ, Nilsson M

Comput Biol Med, 2010 Jan;40(1):81-9.
PMID: 20022595 DOI: 10.1016/j.compbiomed.2009.11.004

The use of vascular intersection aberration as one of the signs when monitoring and diagnosing diabetic retinopathy from retina fundus images (FIs) has been widely reported in the literature. In this paper, a new hybrid approach called the combined cross-point number (CCN) method able to detect the vascular bifurcation and intersection points in FIs is proposed. The CCN method makes use of two vascular intersection detection techniques, namely the modified cross-point number (MCN) method and the simple cross-point number (SCN) method. Our proposed approach was tested on images obtained from two different and publicly available fundus image databases. The results show a very high precision, accuracy, sensitivity and low false rate in detecting both bifurcation and crossover points compared with both the MCN and the SCN methods.

Matched MeSH terms: Retina/pathology*
Local configuration pattern features for age-related macular degeneration characterization and classification

Mookiah MR, Acharya UR, Fujita H, Koh JE, Tan JH, Noronha K, et al.

Comput Biol Med, 2015 Aug;63:208-18.
PMID: 26093788 DOI: 10.1016/j.compbiomed.2015.05.019

Age-related Macular Degeneration (AMD) is an irreversible and chronic medical condition characterized by drusen, Choroidal Neovascularization (CNV) and Geographic Atrophy (GA). AMD is one of the major causes of visual loss among elderly people. It is caused by the degeneration of cells in the macula which is responsible for central vision. AMD can be dry or wet type, however dry AMD is most common. It is classified into early, intermediate and late AMD. The early detection and treatment may help one to stop the progression of the disease. Automated AMD diagnosis may reduce the screening time of the clinicians. In this work, we have introduced LCP to characterize normal and AMD classes using fundus images. Linear Configuration Coefficients (CC) and Pattern Occurrence (PO) features are extracted from fundus images. These extracted features are ranked using p-value of the t-test and fed to various supervised classifiers viz. Decision Tree (DT), Nearest Neighbour (k-NN), Naive Bayes (NB), Probabilistic Neural Network (PNN) and Support Vector Machine (SVM) to classify normal and AMD classes. The performance of the system is evaluated using both private (Kasturba Medical Hospital, Manipal, India) and public domain datasets viz. Automated Retinal Image Analysis (ARIA) and STructured Analysis of the Retina (STARE) using ten-fold cross validation. The proposed approach yielded best performance with a highest average accuracy of 97.78%, sensitivity of 98.00% and specificity of 97.50% for STARE dataset using 22 significant features. Hence, this system can be used as an aiding tool to the clinicians during mass eye screening programs to diagnose AMD.

Matched MeSH terms: Retina/pathology*
Retinal findings in adult leukaemia: correlation with leukocytosis

Jackson N, Reddy SC, Hishamuddin M, Low HC

Clin Lab Haematol, 1996 Jun;18(2):105-9.
PMID: 8866143

The associations between retinal findings and haematological parameters in acute leukaemia are controversial. Sixty-three newly-diagnosed acute leukaemia patients, aged 12-77 years, were studied prospectively for the presence of intra-retinal haemorrhages (IRH), white-centred haemorrhages (WCH), cotton wool spots (CWS) and macular haemorrhages (MH), Thirty-three patients (52.4%) showed at least one retinal abnormality. The prevalence of individual findings was: IRH (30 cases), WCH (20 cases), CWS (5 cases), MH (11 cases). In contrast to previous studies, there was no association between any of these retinal findings and the haemoglobin level or the platelet count. There was a higher median WBC in patients with IRH (68 x 10(9)/l) than in those without IRH (15.4 x 10(9)/l), P = 0.037. When the acute myeloblastic leukaemia cases were considered separately, an association was also found between higher WBC and the presence of WCH and CWS. There was no association between retinal findings and FAB type in the AML cases. We conclude that a high WBC may be at least as important as anaemia and thrombocytopenia in the pathogenesis of the retinopathy of acute leukaemia.

Matched MeSH terms: Retina/pathology*
Fulltext Analysis of the association between CFH Y402H polymorphism and response to intravitreal ranibizumab in patients with neovascular age-related macular degeneration (nAMD)

Mohamad NA, Ramachandran V, Ismail P, Mohd Isa H, Chan YM, Ngah NF, et al.

Bosn J Basic Med Sci, 2018 Aug 01;18(3):260-267.
PMID: 29579408 DOI: 10.17305/bjbms.2018.2493

Pharmacogenetic studies indicate that a variable response to anti-vascular endothelial growth factor (VEGF) therapy in patients with neovascular form of AMD (nAMD) may be due to polymorphisms in the complement factor H gene (CFH). This study is the first to investigate the association between CFH Y402H polymorphism and the response to ranibizumab therapy in Malaysian patients with nAMD. We included 134 patients with nAMD, examined between September 2014 and February 2016. The diagnosis of nAMD was confirmed by ophthalmologic examination, before ranibizumab therapy was started. Each patient received an intravitreal injection of 0.5 mg/0.05 ml ranibizumab following a treat-and-extend (TE) regimen. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were recorded after 3 and 6 months following the first injection and compared with the baseline values. Genotyping of Y402H (rs1061170) polymorphism was performed using PCR-RFLP and the amplified product was digested with MluCI restriction enzyme. Association between the Y402H genotypes and response to treatment was determined by a logistic regression analysis of responder (n = 49) and non-responder (n = 84) group. Significantly worse mean BCVA was observed for the CC genotype compared to the TT + CT genotype in the total sample after 6-month follow-up (p = 0.018). Comparing the baseline and 6-month point measurements, improved mean BCVA was observed in responder group, while worse mean BCVA was recorded for non-responder group. However, our regression analysis, adjusted for confounding factors, showed no significant association between the Y402H genotypes and response to treatment in nAMD patients under the recessive model (p > 0.05). Overall, our results suggest that factors other than Y402H polymorphism may be involved in the progression of nAMD after treatment with anti-VEGF agents, in Malaysian population.

Matched MeSH terms: Retina/pathology
Fulltext Protective Effect of Palm Oil-Derived Tocotrienol-Rich Fraction Against Retinal Neurodegenerative Changes in Rats with Streptozotocin-Induced Diabetic Retinopathy

Sadikan MZ, Nasir NAA, Agarwal R, Ismail NM

Biomolecules, 2020 04 05;10(4).
PMID: 32260544 DOI: 10.3390/biom10040556

: Oxidative stress plays an important role in retinal neurodegeneration and angiogenesis associated with diabetes. In this study, we investigated the effect of the tocotrienol-rich fraction (TRF), a potent antioxidant, against diabetes-induced changes in retinal layer thickness (RLT), retinal cell count (RCC), retinal cell apoptosis, and retinal expression of vascular endothelial growth factor (VEGF) in rats. Additionally, the efficacy of TRF after administration by two different routes was compared. The diabetes was induced in Sprague-Dawley rats by intraperitoneal injection of streptozotocin. Subsequently, diabetic rats received either oral or topical treatment with vehicle or TRF. Additionally, a group of non-diabetic rats was included with either oral or topical treatment with a vehicle. After 12 weeks of the treatment period, rats were euthanized, and retinas were collected for measurement of RLT, RCC, retinal cell apoptosis, and VEGF expression. RLT and RCC in the ganglion cell layer were reduced in all diabetic groups compared to control groups (p < 0.01). However, at the end of the experimental period, oral TRF-treated rats showed a significantly greater RLT compared to topical TRF-treated rats. A similar observation was made for retinal cell apoptosis and VEGF expression. In conclusion, oral TRF supplementation protects against retinal degenerative changes and an increase in VEGF expression in rats with streptozotocin-induced diabetic retinopathy. Similar effects were not observed after topical administration of TRF.

Matched MeSH terms: Retina/pathology*
Fulltext Branch retinal vein occlusion associated with quetiapine fumarate

Yong KC, Kah TA, Ghee YT, Siang LC, Bastion ML

BMC Ophthalmol, 2011;11:24.
PMID: 21867521 DOI: 10.1186/1471-2415-11-24

To report a case of branch retinal vein occlusion in a young adult with bipolar mood disorder treated with quetiapine fumarate.

Matched MeSH terms: Retina/pathology*
Fulltext Diabetic retinopathy: a comprehensive update on in vivo, in vitro and ex vivo experimental models

Sadikan MZ, Abdul Nasir NA, Lambuk L, Mohamud R, Reshidan NH, Low E, et al.

BMC Ophthalmol, 2023 Oct 19;23(1):421.
PMID: 37858128 DOI: 10.1186/s12886-023-03155-1

Diabetic retinopathy (DR), one of the leading causes of visual impairment and blindness worldwide, is one of the major microvascular complications in diabetes mellitus (DM). Globally, DR prevalence among DM patients is 25%, and 6% have vision-threatening problems among them. With the higher incidence of DM globally, more DR cases are expected to be seen in the future. In order to comprehend the pathophysiological mechanism of DR in humans and discover potential novel substances for the treatment of DR, investigations are typically conducted using various experimental models. Among the experimental models, in vivo models have contributed significantly to understanding DR pathogenesis. There are several types of in vivo models for DR research, which include chemical-induced, surgical-induced, diet-induced, and genetic models. Similarly, for the in vitro models, there are several cell types that are utilised in DR research, such as retinal endothelial cells, Müller cells, and glial cells. With the advancement of DR research, it is essential to have a comprehensive update on the various experimental models utilised to mimic DR environment. This review provides the update on the in vitro, in vivo, and ex vivo models used in DR research, focusing on their features, advantages, and limitations.

Matched MeSH terms: Retina/pathology
Fulltext Differential expression and role of hyperglycemia induced oxidative stress in epigenetic regulation of β1, β2 and β3-adrenergic receptors in retinal endothelial cells

Safi SZ, Qvist R, Yan GO, Ismail IS

BMC Med Genomics, 2014;7:29.
PMID: 24885710 DOI: 10.1186/1755-8794-7-29

Aberrant epigenetic profiles are concomitant with a spectrum of developmental defects and diseases. Role of methylation is an increasingly accepted factor in the pathophysiology of diabetes and its associated complications. This study aims to examine the correlation between oxidative stress and methylation of β1, β2 and β3-adrenergic receptors and to analyze the differential variability in the expression of these genes under hyperglycemic conditions.

Matched MeSH terms: Retina/pathology*
Triple Vessel Coronary Artery Disease and Retinal Nerve Fibre Layer Thickness

Neoh YL, Neoh PF, Salleh A, Yusof ZB, Gurusamy B, Ahmad Tajudin LS

Ann Acad Med Singap, 2018 06;47(6):226-229.
PMID: 30019068
Matched MeSH terms: Retina/pathology*
Retinopathy in acute leukaemia at initial diagnosis: correlation of fundus lesions and haematological parameters

Reddy SC, Jackson N

Acta Ophthalmol Scand, 2004 Feb;82(1):81-5.
PMID: 14738490

PURPOSE: To determine the prevalence of retinal changes in newly diagnosed acute leukaemia patients, and to establish the relationship between retinal lesions and haematological parameters in these patients.
METHODS: A total of 127 patients with acute leukaemia (myeloid and lymphoid), of both genders, aged between 13 and 77 years, were examined by an ophthalmologist for retinal changes using direct/indirect ophthalmoscopy within 2 days of diagnosis before starting chemotherapy.
RESULTS: Retinal lesions were seen in 62 cases (49%), with intraretinal haemorrhages being the most common lesion (42%). A high white blood cell count was significantly associated with intraretinal haemorrhages (p = 0.04) and white-centred haemorrhages (p = 0.001), while a low platelet count was significantly associated with intraretinal haemorrhages (p = 0.03) in acute myeloid leukaemia patients.
CONCLUSIONS: A high white blood cell count may be considered as important as a low platelet count in the pathogenesis of leukaemic retinopathy.

Matched MeSH terms: Retina/pathology*
Advanced retinoblastoma in Malaysian children

Sinniah D, Narasimha G, Prathap K

Acta Ophthalmol, 1980 Oct;58(5):819-24.
PMID: 7211270

Twenty children with retinoblastoma are reviewed who were treated at the University Hospital, Kuala Lumpur over a 10-year-period. They constitute 6.6% of childhood malignancies and without exception all presented with advanced disease. Hereditary cases were notably absent in the the series probably because past cases have almost invariably succumbed without an opportunity to transmit the gene. With enucleation and radiotherapy six of the patients have survived from 2 to 12 years. The addition of vincristine and cyclophosphamide has not been associated with improved survival.

Matched MeSH terms: Retina/pathology

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