Intraocular Disorders Research Articles

Review Article: Understanding Influenza-Related Eye Diseases

Eye flu also known as a conjuctivities or red eye is highly contagious disease as well as pink eye is among the most common disease world wild . The prominent system vission. The eye flu which can spread from one person to anotherr person. Opthalmology clinics around the world see a lot of patients with conjuctivities viral conjuctivities followed by bacterial conjuctivies is the most common cause of infection eye flu while allergic and toxin –induced eye flu are among the most common non - infection etiologics . One of the most typical causes of red eyes,conjuctivities strickes people of all ages and sociocconomic background.the majority of infection conjuctivities causes,upto 75% of them are caused by viral conjuctivities.this overviews briefly describe current literature findings ophthalmology related to corunavirus disease that become a worldwide pandemic. Virous account for 80% of all cases of acute cunjunctivities and adenoviruses ; entrovirus and herpes virus are the common causative agent in general , viral conjuctivities spreads easily .Opthalmology clinics around the world see a lot of patient with conjuctivities . severe pain , impaired vision and a painful pupillary reaction are red flags for more serious intraocular disorders that should be taken into account while treating suspected cases of conjunctivitis. Conjunctivitis in children is very contagious ,and if hygiene condition are not observed or treated carelessly,it is easily transferred to a heathly eye or from person to person . bacteria and viruses a head the list of organisms capable of invading the exposed cunjunctiva.

Differential Diagnosis of Leukocoria : A Case Report

Introduction : Leukocoria is an abnormal pupillary reflex more clearly seen after mydriasis or photography. It is often the first sign of a range of serious intraocular disorders, including congenital cataracts, Coats disease, retinoblastoma, Familial Exudative Vitreoretinopathy (FEVR).
 Case Illustration : Baby F, 10 months with chief complaint the vision in both eyes appears defocused since birth. A history of trauma to the head is denied, severe pain (-), a history of similar complaints in the family is denied. Pregnancy history: Mother had hypertension. The patient born spontaneusly at 39-40 weeks of gestation, crying immediately, birth weight 2700 grams. Ophtalmology Status ODS: VA Blink reflex(+), Following light (+), Following object (-), Konjungtiva : hiperemis (-), cornea : clear (+), Pupil : leukocoria (+). Funduscopy examination ODS: Vitreus : cloudy (+), papillae: cannot be assessed, blood vessels: visible images of raised blood vessels, retina: detached (+) retinal layers seen, macula: cannot be assessed. USG ODS: cloudy vitreus with hyperreflectivity moderate to high. Patient was diagnosed with Leucocoria ec Retinal Detachment ec Suspect FEVR differential diagnosis Retinoblastoma Bilateral. CT Scan : A mass with a calcified component in the right and left posterior bulbs, consistent with bilateral retinoblastoma
 Discussion : The clinical history of leukocoria, meaning loss of the normal red retinal reflex, is nonspecific. Key findings here are the normal size of the globes and the presence of calcifications, which are more compatible with retinoblastoma, Coats' disease, or FEVR.
 Conclusion Leucocoria in aterm baby has several differential diagnosis such as retinoblastoma that needs further examination.

A Review on Most Opthalmic Viral Disease Conjunctivitivs (Eye Flu)

Ophthalmology clinics around the world see a lot of patients with conjunctivitis. Severe pain, impaired vision, and a painful pupillary reaction are all red flags for more serious intraocular disorders that should be taken into account while treating suspected cases of conjunctivitis. In patients with unusual findings and a chronic course, it is also important to have a complete medical and ocular history and do a comprehensive physical examination. The existence of a systemic ailment affecting the conjunctiva may be shown by concurrent findings on physical exam and pertinent history. The vast majority of cases of conjunctivitis still originate from viruses. Bacterial conjunctivitis is the second most prevalent cause of infectious conjunctivitis; however it is much less common than viral conjunctivitis. Nearly half of the population experiences allergic conjunctivitis, characterised by symptoms like itching, mucoid discharge, chemosis, and edoema of the eyelids. A patient with conjunctival irritation and discharge who has used preservative-containing eye drops regularly likely has toxic conjunctivitis. Timely diagnosis, proper classification of the various aetiologies, and suitable treatment are essential components of effective management of conjunctivitis.

Dissolvable hybrid microneedle patch for efficient delivery of curcumin to reduce intraocular inflammation

Intraocular inflammation seriously impairs vision, and the effectiveness of intraocular drug delivery is hampered by various physiological barriers, such as the corneal barrier. In this paper, we present a simple approach to fabricating a dissolvable hybrid microneedles (MNs) patch for the efficient delivery of curcumin to treat intraocular inflammatory disorders. Water-insoluble curcumin was first encapsulated into polymeric micelles with high anti-inflammatory capacities, and then were combined with hyaluronic acid (HA) to create a dissolvable hybrid MNs patch using a simple micromolding method. Curcumin was amorphously dispersed within the MNs patch as indicated by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) analyses. According to an in vitro drug release study, the proposed MNs patch provided sustainable drug release over 8 h. Following its in vivo topical application, the MNs patch demonstrated an extended pre-corneal retention time over 3.5 h and exhibited great ocular biocompatibility. Additionally, such MNs patch could reversibly penetrate the corneal epithelium, generating an array of microchannels on the corneal surface, thereby increasing ocular bioavailability. Of greater significance, the use of MNs patch demonstrated the improved therapeutic effectiveness in treating endotoxin-induced uveitis (EIU) in a rabbit model compared to curcumin eye drops via a significant reduction in the infiltration of inflammatory cells such as CD45+ leukocytes and CD68+ macrophages. Overall, the topical application of the MNs patch as an efficient ocular drug delivery system could potentially serve as a promising approach for treating different types of intraocular disorders.

Roth’s spots in leukemia

Roth’s spots are retinal hemorrhages with white or pale centers, which can be seen in numerous conditions. Ocular disorders have been described in 39.3% of patients with diagnosis of leukemia. Incidences of intraocular manifestations are 7.7% in patients of chronic leukemia. Mechanism of retinal hemorrhages is related to hyperviscosity syndrome caused by leukocytosisor direct infiltration. Fundoscopy is a mandatory examination by ophthalmologist in patients of leukemia with intraocular disorders. We present the case of Roth’s spots in a 32-year-old man of chronic myeloid leukemia.

Experimental Autoimmune Uveitis: An Intraocular Inflammatory Mouse Model.

Experimental Autoimmune Uveitis (EAU) is driven by immune cells responding to self-antigens. Many features of this non-infectious, intraocular inflammatory disease model recapitulate the clinical phenotype of posterior uveitis affecting humans. EAU has been used reliably to study the efficacy of novel inflammatory therapeutics, their mode of action and to further investigate the mechanisms that underpin disease progression of intraocular disorders. Here, we provide a detailed protocol on EAU induction in the C57BL/6J mouse - the most widely used model organism with susceptibility to this disease. Clinical assessment of disease severity and progression will be demonstrated using fundoscopy, histological examination and fluorescein angiography. The induction procedure involves subcutaneousinjection of an emulsion containing a peptide (IRBP1-20) from the ocular protein interphotoreceptor retinoid binding protein (also known as retinol binding protein 3), Complete Freund's Adjuvant (CFA) and supplemented with killed Mycobacterium tuberculosis. Injection of this viscous emulsion on the back of the neck is followed by a single intraperitoneal injection of Bordetella pertussis toxin. At the onset of symptoms (day 12-14) and under general anesthesia, fundoscopic images are taken to assess disease progression through clinical examination. These data can be directly compared with those at later timepoints and peak disease (day 20-22) with differences analyzed. At the same time, this protocol allows the investigator to assess potential differences in vessel permeability and damage using fluorescein angiography. EAU can be induced in other mouse strains - both wildtype or genetically modified - and combined with novel therapies offering flexibility for studying drug efficacy and/or disease mechanisms.

Endothelial Ca2+ Signaling, Angiogenesis and Vasculogenesis: Just What It Takes to Make a Blood Vessel

It has long been known that endothelial Ca2+ signals drive angiogenesis by recruiting multiple Ca2+-sensitive decoders in response to pro-angiogenic cues, such as vascular endothelial growth factor, basic fibroblast growth factor, stromal derived factor-1α and angiopoietins. Recently, it was shown that intracellular Ca2+ signaling also drives vasculogenesis by stimulation proliferation, tube formation and neovessel formation in endothelial progenitor cells. Herein, we survey how growth factors, chemokines and angiogenic modulators use endothelial Ca2+ signaling to regulate angiogenesis and vasculogenesis. The endothelial Ca2+ response to pro-angiogenic cues may adopt different waveforms, ranging from Ca2+ transients or biphasic Ca2+ signals to repetitive Ca2+ oscillations, and is mainly driven by endogenous Ca2+ release through inositol-1,4,5-trisphosphate receptors and by store-operated Ca2+ entry through Orai1 channels. Lysosomal Ca2+ release through nicotinic acid adenine dinucleotide phosphate-gated two-pore channels is, however, emerging as a crucial pro-angiogenic pathway, which sustains intracellular Ca2+ mobilization. Understanding how endothelial Ca2+ signaling regulates angiogenesis and vasculogenesis could shed light on alternative strategies to induce therapeutic angiogenesis or interfere with the aberrant vascularization featuring cancer and intraocular disorders.

Laser flare-cell photometer: principle and significance in clinical and basic ophthalmology.

A slit-lamp examination is an indispensable and essential clinical evaluation method in ophthalmology, but, it is qualitative subjective. To complement its weaknesses in making a quantitative evaluation of flare intensity and number of cells in the aqueous humor in the eye, we invented the laser flare-cell photometer in 1988. The instrument enables a non-invasive quantitative evaluation of flare intensity and number of cells in the aqueous with good accuracy and repeatability as well as maneuverability equal to slit-lamp microscopy. The instrument can elucidate the pathophysiology in the blood-aqueous barrier (BAB) function in a variety of ocular disorders. The accuracy of the instrument makes it possible to investigate not only the pathophysiology of intraocular disorders but also the effects of various drugs and surgical procedures in BAB. The instrument does not only lighten the burden on patients in clinical examinations and study but it also helps minimize the sacrifice of experimental animals and improves the reliability of the results by minimizing inter-individual variations through its good repeatability. Here I shall relate how the instrument has been applied to clinical and basic studies in ophthalmology and what novel knowledge its application contributed to pathophysiology in ophthalmology.

SIRT1 activation protects against autoimmune T cell-driven retinal disease in mice via inhibition of IL-2/Stat5 signaling

Sirtuins are a mammalian family of NAD+-dependent histone deacetylases that regulate cell function and survival as well as regulating cell responses under inflammatory conditions. SIRT1 activator treatment in vitro using mouse pLN cells, normal human and ocular Behçet's disease donor PBMC resulted in suppressed T cell proliferation and pro-inflammatory cytokine production. Our data suggest a novel mechanism by which SIRT1 activators contribute to suppression of T cell proliferation by both down regulating STAT5A/B expression and suppression of pSTAT5A/B signaling in response to IL-2. Experimental autoimmune uveoretinitis (EAU) in B10.RIII mice is an antigen-specific cell-mediated model of human intra-ocular inflammatory disease. Infiltrating CD4+ T cells in the retina secrete both IFN-γ and IL-17 and are accompanied by inflammatory granulocytes and macrophages which together result in retinal destruction. Oral SIRT1 activator treatment administered to EAU mice suppressed disease with an accompanying reduction in retinal leukocytic infiltrate, suppressed antigen-specific T cell responses and marked suppression of innate and adaptive pro-inflammatory cytokine production in the eye including IL-6, IL-17A and IFN-γ. In vivo SIRT1 activator treatment also suppressed production of IL-17A, IL-17F, IL-6, TGFβ and IL-22 by pLN cells. Oral SIRT1 activator treatment administered to mice during the efferent phase (days7–14) of EAU was effective at suppressing disease. These observations demonstrate that SIRT1 activation is anti-inflammatory in nature and future targeted activation of SIRT1 shows promise as a potential treatment for non-infectious intra-ocular disorders such as uveitis associated with Behçets disease.

Detection of Candida and Aspergillus species DNA using broad-range real-time PCR for fungal endophthalmitis

The goal of this work is to establish a broad-range real-time polymerase chain reaction (PCR) diagnostic system for ocular fungal infection and to measure Candida and Aspergillus DNA in the ocular fluids obtained from unknown uveitis/endophthalmitis patients. After obtaining informed consent, intraocular fluids (aqueous humor and vitreous fluid samples) were collected from 54 patients with idiopathic uveitis or endophthalmitis. Samples were assayed for Candida or Aspergillus DNA using broad-range (18S rRNA sequences) quantitative real-time PCR. Candida or Aspergillus DNA was detected in seven out of 54 patient ocular samples (13%). These PCR-positive samples showed significantly high copy numbers of Candida or Aspergillus DNA. On the other hand, fungal DNA was not detected in any of the other 46 samples collected from these idiopathic uveitis or endophthalmitis patients. In the one PCR-negative case, PCR did not detect any fungal genome in the sample, even though this patient was clinically suspected of having Candida endophthalmitis. Real-time PCR results were negative for fungal DNA in the bacterial endophthalmitis patients and in various uveitis patients. In addition, fungal DNA was also not detected in patients without ocular inflammation (controls). Analysis of ocular samples by this broad-range real-time PCR method can be utilized for rapid diagnosis of patients suffering from unknown intraocular disorders such as idiopathic uveitis/endophthalmitis.

Aqueous humor vascular endothelial growth factor in dogs: association with intraocular disease and the development of pre‐iridal fibrovascular membrane

To examine the concentrations of vascular endothelial growth factor (VEGF) in aqueous humor of dogs with intraocular disease and to evaluate the association of aqueous humor VEGF with pre-iridal fibrovascular membrane (PIFM) formation. Two hundred and twenty six aqueous humor samples and 101 plasma samples were collected from 178 dogs with a variety of intraocular diseases (including cataract, primary glaucoma, uveitic glaucoma, aphakic/pseudophakic glaucoma, retinal detachment, lens luxation, and intraocular neoplasia), and aqueous humor was collected from 13 ophthalmically normal control dogs. Systemic disease status and administration of select medications were recorded. Aqueous and plasma VEGF was assayed via enzyme-linked immunosorbant assay validated for canine VEGF. Available histopathology samples were examined for the presence of PIFM. Where present, PIFMs were categorized as none, cellular, vascular or fibrous, and fibrovascular. Data were evaluated by mixed model anova, with application of Tukey-Kramer adjustment for multiple comparisons. There was no association between aqueous humor and plasma VEGF levels. Compared with normal controls, aqueous humor VEGF was significantly elevated for all intraocular diseases (P < 0.05) except for primary and diabetic cataracts. Systemic disease and administered medications had no significant effect on aqueous humor VEGF concentration. Compared to dogs without PIFM, aqueous humor VEGF was significantly higher in dogs with fibrovascular PIFM (P = 0.001), but not cellular (P = 0.1704) or fibrous/vascular PIFM (P = 0.0667). These findings confirm that VEGF is commonly elevated in aqueous humor of dogs with intraocular disease and likely plays a role in the causation or progression of a variety of intraocular disorders, including the development of PIFM.

Intraocular complications of IFN-α and ribavirin therapy in patients with chronic viral hepatitis C

We report a panel of severe inflammatory and vascular intraocular disorders occurring during interferon-alpha (IFN-alpha) treatment in eight hepatitis C virus (HCV)-infected patients. These events include three cases of Vogt-Koyanagi-Harada like (VKH) disease (an association of panuveitis, retinal detachment, ear and meningeal detachment and skin and hair changes), two cases of central retinal vein occlusion, one case of central retinal artery occlusion, one case of severe hypertensive retinopathy and one case of bilateral ischemic optic neuropathy with severe visual impairment. Rare as they are, such severe ophthalmological complications require a close follow-up of HCV-infected patients under IFN-alpha treatment with ophthalmological monitoring if any ocular manifestation occurs.

Intravitreal steroids in the management of macular oedema

The use of intravitreal corticosteroids in the management of macular oedema has recently gained widespread acceptance. New long-acting steroid preparations and methods of delivery have facilitated the use of these new modalities. This review describes the various types of macular oedema for which this therapeutic option is used and the results.

Drug delivery from ocular implants

Developing an intraocular drug delivery system (DDS) is urgently needed because most vitreoretinal diseases are refractory to conventional pharmacological approaches; eye drops and systemically administered drugs cannot deliver therapeutic drug concentrations into vitreoretinal tissue. Intraocular DDSs address this problem. Intraocular sustained-drug release via implantable devices or injectable microparticles has been investigated to treat vitreoretinal diseases. A nonbiodegradable implant was first used in 1996 for cytomegalovirus retinitis secondary to the acquired immunodeficiency syndrome. Biodegradable implants, composed of hydrophilic or hydrophobic polymers, in the shape of rods, plugs, discs or sheets have been investigated. An injectable rod is presently being assessed in a Phase III trial to treat macular oedema secondary to diabetic retinopathy or branch-retinal vein occlusion. Intraocular DDSs using a biodegradable implant may soon be successfully used to treat serious intraocular disorders.

Anterior chamber depth and intraocular pressure following panretinal argon laser photocoagulation for diabetic retinopathy

Anterior chamber depth and intraocular pressure following panretinal argon laser photocoagulation for diabetic retinopathy

Preseptal Abscess Formation Following Ocular Cryotherapy for Behçet's Uveitis

A 42-year-old man with Behçet's disease developed a rapidly growing mass under his right lower eyelid a week after transconjunctival cryotherapy. He underwent surgical drainage of the mass following imaging studies. Magnetic resonance imaging scans demonstrated the abscess, which did not violate the orbital septum. Cultures from drained material yielded Staphylococcus aureus. He recovered completely with systemic antibiotics. Preseptal abscess may occur as a complication of intense transconjunctival cryotherapy for intraocular disorders, and patients should be followed closely within the first few weeks postoperatively.

Inhibition of cell-induced vitreous contraction by synthetic peptide derived from the collagen receptor binding sequence.

Cell-mediated tractional retinal detachment (TRD) is the end result of various intraocular proliferative disorders. Interactions between cells and extracellular matrix via cellular surface receptors, integrins, play an important role. Anti-adhesion therapy has been suggested as a promising way to treat the integrin-dependent pathological events. We tested three synthetic peptides, Gly-Arg-Gly-Asp-Ser (GRGDS), derived from the fibronectin receptor binding domain; Try-Ile-Gly-Ser-Arg (YIGSR), from the laminin receptor binding domain, and Ala-Asp-Gly-Glu-Ala (ADGEA), from the collagen receptor binding domain, to evaluate their inhibitory effect on cell-mediated matrix attachment and vitreous contraction in vitro, and on cell-induced TRD in rabbit eyes in vivo. Indirect immunofluorescent stain demonstrated both bovine retinal pigment epithelial (RPE) cells and rabbit dermal fibroblasts expressed the alpha 2 beta 1, alpha 5 beta 1 and alpha 6 beta 1 integrins, the collagen, fibronectin, and laminin receptors, respectively. GRGDS exhibited a broad spectrum of inhibitory activity on RPE cell attachment to extracellular matrices. YIGSR specifically inhibited RPE cell attachment to laminin, whereas ADGEA inhibited RPE cell attachment to collagen type I and IV. ADGEA inhibited RPE cell-induced vitreous contraction in a dose-dependent manner, whereas GRGDS and YIGSR had no effect. ADGEA (1250 micrograms/mL) delayed the development of TRD but did not prevent it. ADGEA was nontoxic to cells and retina, as demonstrated by cytotoxicity tests and histological examination. The synthetic peptide, ADGEA, and its analogs may be potential candidates for the treatment of cell-mediated collagenous contraction in the ocular tissues.

Immune response to specific molecules of the retina in proliferative vitreoretinal disorders

In recent years, several reports have contributed to a growing suspicion that there is immunologic involvement in proliferative intraocular disorders such as proliferative vitreoretinopathy and proliferative diabetic retinopathy. Immune privilege, as in the brain, ovary and testis, also exists in the eye. Therefore, immune responses to unique molecules of the eye, e.g. retinal S-antigen (S-Ag), which the immune system never learns to regard as "self", are possible. This study describes the presence of S-Ag, a major soluble photoreceptor protein involved in the visual transduction cascade, in pathological vitreous. We employed indirect immunoblotting, with human retina as substrate, and demonstrated the occurrence of antiretinal antibodies in the sera of a series of patients with proliferative vitreoretinal disorders. Immunoblot analysis of physiological retina and lyophilized S-Ag, revealed this protein as a target molecule of the immunological involvement of the retina. Further immunochemical investigation, however, must clarify whether this autoimmune reaction is the cause, a consequence, or an aggravating factor of the disease. As we come to understand the cellular and molecular mechanism, a new generation of therapeutic strategies may be envisioned.

Origin of fibronectin in epiretinal membranes of proliferative vitreoretinopathy and proliferative diabetic retinopathy.

Fibronectins, high molecular multifunctional glycoproteins of the extracellular matrix and plasma, have been a popular area of research in the pathogenesis of proliferative disorders of the retina. Several immunohistochemical studies have revealed that fibronectin is a major constituent of epiretinal membranes and that the cell types involved in proliferative intraocular disorders may synthesise it. However, owing to the fact that plasma and cellular fibronectin are similar in their overall structure, the origin of fibronectin in epiretinal membranes has not yet been clearly defined. In this study, we used two monoclonal antibodies: FN-3, which recognises an extra domain present in the cellular but not plasma form of fibronectin; and FN-4, which reacts with an antigenic site on both plasma and cellular fibronectin. In 37 epiretinal membranes obtained from eyes with proliferative vitreoretinopathy and proliferative diabetic retinopathy, we demonstrated the presence of cellular fibronectin, thus indicating local production. The significantly stronger and positive immunostain with FN-4 in the same specimens suggests the colocalisation of plasma fibronectin, that may be derived from the breakdown of the blood-retinal barrier and trapped in membranes during their formation. In pathological vitreous we demonstrated both types of fibronectin by western blot analysis.

Intraocular pressure and vasospastic disorders in normal tension glaucoma

Intraocular pressure and vasospastic disorders in normal tension glaucoma