Clinical Signs Of Ocular Disease Research Articles

Koala ocular disease grades are defined by chlamydial load changes and increases in Th2 immune responses

IntroductionThis study employs bulk RNA sequencing, PCR, and ELISA assays to analyze the pathological factors affecting the outcomes of C. pecorum ocular infections in koalas. It investigates the immune responses and gene expression profiles associated with various stages of koala ocular chlamydiosis.MethodsA cohort of 114 koalas from Queensland, Australia were assessed, with 47% displaying clinical signs of ocular disease. Animals were classified into three cohorts: acute active disease (G1), chronic active disease (G2), and chronic inactive disease (G3), along with subclinical Chlamydia pecorum positive (H2) and healthy (H1) cohorts.ResultsAnalysis of clinical, microbiological, humoral immune and cellular immune biomarkers revealed varying chlamydial loads and anti-chlamydial IgG levels across disease grades, with a negative correlation observed between ocular chlamydial load and anti-chlamydial IgG. Koala ocular mucosa gene expression analysis from 27 koalas identified shared expression pathways across disease cohorts, with a significant upregulation of IFNγ expression and tryptophan metabolism in all disease stages.DiscussionThese findings help elucidate immune response dynamics and molecular pathways underlying koala ocular chlamydiosis, providing insights crucial for disease management strategies.

Effects of platelet-rich plasma on corneal re-epithelization and metalloproteinase expression in the cornea of sheep with experimentally-induced infectious keratoconjunctivitis.

Infectious bovine keratoconjunctivitis is the most crucial ophthalmic disease among ruminants worldwide. Moraxella is the bacteria generally associated with this disease and leads to keratitis, conjunctivitis, corneal ulcers, or blindness. Platelet-rich plasma (PRP) effects in corneal ulcers and different ocular superficial diseases in animals and humans are beneficial and enhance rapid healing and improvement, but the effects in infectious keratoconjunctivitis in ruminants are uncertain. This study aimed to examine the effect of PRP on re-epithelization, corneal tissue, clinical signs, and matrix metalloproteinase (MMP) expression in sheep with infectious keratoconjunctivitis. Eighteen sheep were divided into three groups and subjected to a disease-induction experiment. Group 1 (G1) was administered 1.0 mL PRP subconjunctivally, Group 2 (G2) was administered 1.0 mL PRP subconjunctivally and 50 μL gentamicin drops, and the control group (CG) was administered 50 μL saline solution topically every 12 h. Clinical ophthalmologic examination, fluorescein staining, and photography were carried out. Ulcerated areas were measured employing J-Image software. Five and eleven days following the procedure, half of the animals from each group were euthanized, and their corneas were evaluated by histopathology and zymography. Control Group and G2 epithelialized more rapidly. The CG exhibited fewer clinical signs of ocular disease. In histopathological analysis, in G2, alterations were observed only in the epithelium. The CG and G1 exhibited alterations in the epithelium, stroma, and Descemet's membrane. In zymography, a decline in MMP-2 expression in the animals treated with PRP was detected. Matrix metalloproteinase-9 was significantly expressed in the animals treated with PRP monotherapy, whereas PRP + gentamicin and CG caused a decrease. Platelet-rich plasma alone did not demonstrate any beneficial effect on re-epithelialization, a decline in clinical signs, tissue alterations, and expression of metalloproteinases. Platelet-rich plasma combined with gentamicin was capable of suppressing MMPs, primarily MMP-9, but do not display positive effects in re-epithelization, reduction of clinical signs, or tissue effects. These outcomes are similar to those discovered in untreated animals, so the use of PRP in patients with infectious keratoconjunctivitis does not offer greater benefits in sheep. Additional research is required to validate the results of PRP use in natural disease presentation.

Development of a chlamydial vaccine for koalas : Protection against infection and disease

Abstract Wild koala populations continue to experience serious declines as a result of several threatening factors including, (i) loss of habitat, (ii) motor vehicle trauma; (iii) dog attacks; (iv) Chlamydia. Chlamydial infections are associated with diseases ranging from ocular disease leading to blindness, as well as urinary and genital tract disease, leading to female infertility. Modeling shows that targeting chlamydial disease would have a major impact on stabilising population decline. Our studies have demonstrated that koalas can be safely immunized with a vaccine containing a mixture of chlamydial major outer membrane protein (MOMP) antigens combined with a single dose subcutaneous regime. We conducted a wild koala field trial and observed strong, specific and long-lasting immune responses in the vaccinated koalas; high titre antibody responses (as measured by ELISA and also in vitro neutralisation) as well as Chlamydia-specific cytokine responses (interferon-gamma and IL-17 in particular). For animals which were Chlamydia PCR positive at the time of vaccination, we observed a significant reduction in their infection PCR load. We also observed protection from progression to clinical disease in the vaccinated animals. We also conducted a small trial to vaccinate animals which already have clinical signs of ocular disease. Instead of the normal practice of administering antibiotics (chloramphenicol, daily for 28 days, which severely disrupts the animal’s gut microbiome) we vaccinated four animals with a single dose, 3-MOMP vaccine. For all vaccinated animals, their Chlamydia PCR load decreased, and for 6 of the 7 animals, ocular disease regressed and the animals could be released back into the wild without further treatment.

Treatment of Chlamydia-associated ocular disease via a recombinant protein based vaccine in the koala (Phascolarctos cinereus)

Koalas (Phascolarctos cinereus) are affected by debilitating chlamydial disease that can lead to blindness, infertility, and death. The causative agent is the intracellular bacterium Chlamydia pecorum. While antibiotics can be used to treat koala chlamydial infection, they are often ineffective or cause severe dysbiosis to the animal's unique gut flora. Recent work has progressed on the development of a protective vaccine for Chlamydia in the koala. This study demonstrates that the use of a vaccine can have a positive effect in koalas already with clinical signs of ocular disease, suggesting a possible therapeutic effect and an alternative to antibiotic therapy.

Cytokine and chemokine profiles of aqueous humor and serum in horses with uveitis measured using multiplex bead immunoassay analysis

ObjectiveTo determine whether horses with clinically diagnosed Equine Recurrent Uveitis (ERU) and those with Leptospirosis infection have a specific cytokine profile in their aqueous humor (AH) and serum that differs from horses with uveitis secondary to other ocular inflammatory processes and from horses with normal eyes. Animals studiedTwenty-five client-owned horses with uveitis that were presented to the North Carolina State University Ophthalmology Service, and four University-owned horses without history or clinical signs of ocular disease. ProcedureSamples of AH and serum were obtained from horses with ERU (n=13), acute or non-recurrent uveitis (UV; n=7), uveitis secondary to infectious keratitis (IK; n=5), and normal eyes (N; n=4). Cytokine levels in AH and serum were quantified using a multiplex bead immunoassay. Leptospiral antibody titers in serum and AH and PCR for Leptospiral DNA in AH were performed. ResultsIn the AH of horses with ERU, increased levels of IL-1a, IL-4, IL-6, IL-8, IL-12p70, FGF-2, G-CSF, and RANTES were measured compared to UV, IK and N eyes, but the differences were not significant. However, IL-10 was significantly higher in ERU eyes compared to IK and N (P=0.029; 0.013), and IP-10 in ERU eyes was significantly higher than in UV and N (P=0.004). Furthermore, MCP-1 was significantly higher in ERU than N (P=0.04). In the serum, increased levels of IL-1a, IL-4, IL-6, IL-8, IL-12p70, fractalkine, and G-CSF were measured in horses with ERU, but the levels were not significantly higher than those observed in UV, IK, or N horses. However, serum IP-10 levels in horses with ERU were significantly higher than in UV and N horses (P=0.005) and MCP-1 levels were significantly higher in ERU than N (P=0.03). Horses with marked ocular inflammation had significantly higher serum levels of G-CSF, IL-1a, fractalkine, IL-13, IL-4, IL-17a, IL-12p70, IFN-γ, and MCP-1. Elevated IL-10 in AH was significantly associated with disease chronicity, both overall and in ERU eyes (P=0.049), and in horses with positive ocular leptospiral titers or leptospiral PCR, significant elevations of IL-10 (P=0.0018; 0.0032) and IP-10 (P=0.0342; 0.043) were detected in the AH compared to leptospiral negative eyes. ConclusionsThe anti-inflammatory cytokine IL-10 and the pro-inflammatory cytokine IP-10 appear to play an important role in ERU. Further studies are needed to further clarify and characterize cytokine profiles of specific ocular inflammatory diseases, but multiplex bead immunoassay technology shows promise as a diagnostically valuable tool.

Baseline assessment of ophthalmic parameters in the greater one-horned rhinoceros (Rhinoceros unicornis).

Five healthy captive greater one-horned rhinoceroses (Rhinoceros unicornis) were evaluated with standing sedation (detomidine hydrochloride 20-30 mg and butorphanol tartrate 50-60 mg per animal) to determine baseline values for tear production, intraocular pressure (IOP), conjunctival flora, and ocular anatomy using brightness mode transpalpebral ultrasonography with a 4- to 7-MHz broadband curvilinear transducer. The mean Schirmer tear test I value was 18.2 ± 3.49 mm/min. The mean IOP measured using applantation tonometry was 31.2 ± 6.62 mm Hg. Ocular biometry measurements were the following: axial length 2.61 ± 0.11 cm; corneal thickness 0.13 ± 0.01 cm; anterior segment depth 0.28 ± 0.06 cm; lens depth 0.70 ± 0.11 cm; and posterior segment depth 1.46 ± 0.13 cm. These values indicate that the globe is smaller than that of the domestic horse. All eight conjunctival swabs cultured bacterial and fungal microorganisms, with the most common being Staphylococcus spp. (57%). All bacterial isolates were considered to be commensal organisms due to the presence of mixed bacterial populations and lack of clinical signs of ocular disease. The data collected in this study should provide veterinarians with baseline information to assist in the diagnosis of ophthalmic conditions in the greater one-horned rhinoceros.

Functional Hierarchy of Herpes Simplex Virus Type-1 Membrane Proteins in Corneal Infection and Virus Transmission to Ganglionic Neurons

Purpose: To determine the relative importance of viral glycoproteins gK, gM, gE and the membrane protein UL11 in infection of mouse corneas and ganglionic neurons.Methods: Mouse eyes were scarified and infected with herpes simplex virus (HSV)-1(F), gE-null, gM-null, gK-null, or UL11-null viruses. Clinical signs of ocular disease were monitored daily. Virus shedding was determined at 24, 48 and 72 h post infection. Viral DNA within trigeminal ganglia (TG) was quantified by quantitative PCR at 30 d post infection.Results: The gE-null virus replicated as efficiently as the parental virus and formed viral plaques approximately half-the-size in comparison with the HSV-1(F) wild-type virus. The UL11-null and gM-null viruses replicated approximately one log less efficiently than the wild-type virus, and formed plaques that were on average one-third the size and one-half the size of the wild-type virus, respectively. The gK-null virus replicated more than 3-logs less efficiently than the wild-type virus and formed very small plaques (5–10 cells). Mice infected with the wild-type virus exhibited mild clinical ocular symptoms, while mice infected with the mutant viruses did not show any significant ocular changes. The wild-type virus produced the highest virus shedding post infection followed by the gM-null, gE-null and UL11-null viruses, while no gK-null virus was detected at any time point. All TG collected from mice infected with the wild-type virus and 6-of-10 of TG retrieved from mice infected with the UL11-null virus contained high numbers of viral genomes. The gE-null and gM-null-infected ganglia contained moderate-to-low number of viral genomes in 4-of-10 and 2-of-10 mice, respectively. No viral genomes were detected in ganglionic tissues obtained from gK-null eye infections.Conclusions: The results show that gK plays the most important role among gM, gE and UL11 in corneal and ganglionic infection in the mouse eye model.

A Replication Competent HSV-1(McKrae) with a Mutation in the Amino-terminus of Glycoprotein K (gK) is Unable to Infect Mouse Trigeminal Ganglia after Cornea Infection

Purpose: To determine the role of the amino terminus of herpes simplex virus-1 (HSV-1) glycoprotein K (gK) in corneal infection, neuroinvasion, and establishment of virus latency in trigeminal ganglia of mice.Methods: The recombinant virus HSV-1 (McKΔgK31-68) was constructed by engineering gK genes encoding gK lacking 38 amino acids immediately after the gK signal sequence. A rescued virus was also produced. Mouse eyes were scarified and infected with 105 plaque forming units (PFU) in each eye. Clinical signs of ocular disease were monitored daily. Thirty days postinfection trigeminal ganglia were collected and processed for quantitative PCR (qPCR) analysis of viral DNA and recovery of infectious virions by cell culture of ganglionic tissues.Results: Deletion of the amino terminus of gK encoded by the McKΔgK31-68 mutant virus did not substantially affect its replication kinetics on African green monkey kidney cells (Vero), while it reduced cell-to-cell spread. McK viral infection of scarified mouse corneas with 105 PFU produced severe ocular disease. In contrast, McKΔgK31-68 viral infection with 105 PFU produced no significant ocular disease symptoms. All ganglia from mice infected with the McK virus produced high numbers of infectious virions upon explant culture in Vero cells, in agreement with qPCR results detecting high number of HSV-1 viral DNA in ganglionic tissues. In contrast, qPCR failed to detect any viral genomes in McKΔgK31-68 ganglia, while two of the ten ganglia revealed the presence of low numbers of infectious virions upon explant culture in Vero cells.Conclusions: The results show that the amino terminus of gK is essential for neuroinvasiveness and acute herpes keratitis in the mouse eye model. It is likely that gK is involved in efficient infection of axonal termini, since mouse eye scarification provided a direct access to the high density of neuronal axons innervating mouse corneas.

Capturing Age-Related Changes in Functional Contrast Sensitivity With Decreasing Light Levels in Monocular and Binocular Vision

It is challenging to separate the effects of normal aging of the retina and visual pathways independently from optical factors, decreased retinal illuminance, and early stage disease. This study determined limits to describe the effect of light level on normal, age-related changes in monocular and binocular functional contrast sensitivity. We recruited 95 participants aged 20 to 85 years. Contrast thresholds for correct orientation discrimination of the gap in a Landolt C optotype were measured using a 4-alternative, forced-choice (4AFC) procedure at screen luminances from 34 to 0.12 cd/m(2) at the fovea and parafovea (0° and ±4°). Pupil size was measured continuously. The Health of the Retina index (HRindex) was computed to capture the loss of contrast sensitivity with decreasing light level. Participants were excluded if they exhibited performance outside the normal limits of interocular differences or HRindex values, or signs of ocular disease. Parafoveal contrast thresholds showed a steeper decline and higher correlation with age at the parafovea than the fovea. Of participants with clinical signs of ocular disease, 83% had HRindex values outside the normal limits. Binocular summation of contrast signals declined with age, independent of interocular differences. The HRindex worsens more rapidly with age at the parafovea, consistent with histologic findings of rod loss and its link to age-related degenerative disease of the retina. The HRindex and interocular differences could be used to screen for and separate the earliest stages of subclinical disease from changes caused by normal aging.

Conjunctivitis, rhinitis, and sinusitis in cliff swallows (Petrochelidon pyrrhonota) found in association with Mycoplasma sturni infection and cryptosporidiosis

Fledgling cliff swallows were cared for at a rehabilitation facility when clinical signs of ocular disease, characterized by conjunctivitis, epiphora, and hyperaemia of palpebrae and nictitans, were recognized. Treatment consisted of topical and oral antibiotic therapy and one topical steroid administration. However, one cliff swallow died and three were killed due to poor therapeutic response. Conjunctival swabs were obtained ante-mortem from the three cliff swallows and were submitted for mycoplasma culture and molecular diagnostics. Heads of the three birds were fixed in 10% neutral buffered formalin and submitted for histopathologic examination of oculonasal tissues. Mycoplasma cultures and molecular evaluation of isolates identified Mycoplasma sturni, but not Mycoplasma gallisepticum, from each specimen. Histopathologic examination revealed lymphoplasmacytic conjunctivitis, rhinitis and infraorbital sinusitis with follicular lymphoid hyperplasia, epithelial hyperplasia, and protozoal stages compatible with Cryptosporidium spp. arranged in and along the apical surfaces of epithelial cells. Identification of concurrent M. sturni and Cryptosporidium spp. infections in these cliff swallows demonstrates an alternative infectious condition that can produce gross and microscopic lesions comparable with those commonly observed in M. gallisepticum infections of house finches and other passerine species. Conjunctivitis associated with M. sturni and Cryptosporidium spp. in cliff swallows may represent an emerging disease risk to a naïve, high-density and colonial species such as colony-nesting cliff swallows.

Electrophysiological studies in American Quarter horses with neuroaxonal dystrophy

Neuroaxonal dystrophy (NAD) is a disease characterized by the sudden onset of neurologic signs in horses ranging from 4 to 36 months of age. Equine degenerative myeloencephalopathy (EDM), a disease that has been associated with low vitamin E concentrations, is considered a more advanced form of NAD. The objective of this report is to describe the electrophysiological features of NAD/EDM in American Quarter horses (QHs). HORSES: Six NAD/EDM-affected QHs and six unaffected QHs were evaluated by ophthalmic examination and electroretinography. Five of the NAD/EDM-affected QH and five unaffected QHs were also evaluated by electroencephalography (EEG). Ophthalmic examination, ERGs, and EEGs were unremarkable in NAD/EDM cases. Neuroaxonal dystrophy/EDM does not appear to cause clinical signs of ocular disease or functional ERG/EEG deficits in QHs.

Retinal detachment in horses: 40 cases (1998–2005)

To determine clinical features, ophthalmic examination findings, etiology, treatment, and outcome of horses diagnosed with retinal detachment (RD). Forty horses, presented to the North Carolina State University and The Ohio State University Veterinary Teaching Hospitals from 1998 to 2005 that were diagnosed with RD. PROCEDURE(S): Horses with documented RD, confirmed either on ophthalmic examination or by ultrasonography, and with a complete medical record were included. Information retrieved from the medical records included signalment, presenting complaint, duration of clinical signs, ophthalmologic examination findings, diagnostics performed, identified cause of the retinal detachment, treatment given, and outcome. Forty horses (46 eyes) were diagnosed with RD. Mean +/- SD duration of clinical signs of ocular disease was 10.5 +/- 14.7 months. Thirty-four horses presented with unilateral involvement, 6 with bilateral, 14 with partial and 32 with complete RD. Ultrasonography was used to make the diagnosis in 26 eyes, while RD was diagnosed on routine ocular examination in 20 eyes. Bullous RD was the only type of RD observed, although small vitreal traction bands were considered secondary to the underlying inflammation or trauma. RD caused by equine recurrent uveitis (ERU) was diagnosed in 27 of 40 (67.5%) horses. Trauma-induced RD involved 10 of the 40 horses (25%). Presenting problems included known ERU (n = 16), acute or progressive vision loss (n = 9), known ocular trauma (n = 6), cataract (n = 6), and a cloudy cornea (n = 3). No horses regained vision after RD despite therapy. Many eyes were enucleated or eviscerated, or the horses were euthanized. Seven eyes with complete RD were noted to be unchanged and comfortable with medical therapy. The visual prognosis of RD in horses is grave; however, horses with nontraumatic RD (most commonly ERU) may be able to maintain a comfortable but blind globe with anti-inflammatory medical therapy.

Reduced retinal vascularization in children with growth hormone deficiency.

The neovascularization in diabetic retinopathy is believed to involve locally produced angiogenic factors. In addition, there are indications that GH may influence retinal vascularization. To investigate the role of GH in retinal vascularization, we examined the retinal vascular pattern in children with congenital GH deficiency. Retinal vessel morphology was evaluated by digital image analysis of ocular fundus photographs in 39 children (5 girls and 34 boys, aged 3.6-18.7 yr) with congenital GH deficiency, and it was compared to that of 100 healthy controls. Twenty children had received GH treatment (0.1 IU/kg daily). All children were born at term, and none of the children had any clinical signs of ocular disease or reduced vision. Children with GH insufficiencies, regardless of whether they were treated with GH, had a significantly lower number of vascular branching points than the reference group (P < 0.0001). Thirty-three percent of the GH-insufficient individuals had a number of vascular branching points less than or equal to the fifth percentile of the reference group. The reduced retinal vascularization observed in children with congenital GH deficiency suggests that GH may be of importance for angiogenesis.