Corneal Vascularization Research Articles

Investigation of corneal autoantibodies in horses with immune mediated keratitis (IMMK)

Immune mediated keratitis (IMMK) is primarily a non-ulcerative keratitis in horses causing intermittent ocular pain, eventually resulting in visual impairment. Affected horses typically respond to immunomodulatory treatment. However, the underlying cause of the disease remains enigmatic. The current study was undertaken to investigate the presence of autoantibodies in horses with immune mediated keratitis. Using 28 horses with IMMK and 27 healthy controls screening for serum autoantibodies against the corneal proteome using indirect immunofluorescence, one-dimensional (1DE) and two-dimensional electrophoresis (2DE) with subsequent western blot analysis was performed followed by mass spectrometric identification of bands or spots of interest. Indirect immunofluorescence did not reveal a difference in immune response towards corneal proteins between healthy horses and those with IMMK. Using western blot analysis some horses affected by IMMK (4/28) showed a single band (1D) or a single spot (2DE) (5/28) not detected in healthy controls. The corresponding spot was identified as maspin (SERPINB5), a protein responsible for the inhibition of corneal vascularisation, cell migration and cell adhesion to the extracellular matrix. Tests with a recombinant human protein commercially available did not verify blot findings, but the human protein may not be fully cross-reactive. Still, maspin might play a role in some cases of equine IMMK. Further research is needed to clarify the etiology of this disease.

Effect of Histone Deacetylase Inhibitor, Butyroyloxymethyl-Diethyl Phosphate (AN-7), on Corneal Neovascularization in a Mouse Model.

To examine whether butyroyloxymethyl-diethyl phosphate (AN-7), a histone deacetylase inhibitor, inhibits chemically induced corneal neovascularization (NV) in mice. Corneal NV was induced in the right eye of male C57BL mice by application of a mixture of 75% silver nitrate and 25% potassium nitrate to the corneal center. Immediately thereafter, the mice were randomized into 2 groups, receiving an intraperitoneal injection of AN-7 or saline, which served as control. Corneal NV was evaluated at constant time intervals from the corneal injury by corneal photographs and the area of corneal NV was measured. Centricity and density of the corneal vascularization were graded. Corneal flat mounts blood vessels staining and histological studies were performed on day 10. Unpaired t-test was used for group comparisons. The corneal neovascular area was statistically significantly reduced by AN-7 treatment on days 10 and 14 postinjury and compared with the untreated group. The centricity and density of the corneal NV between treated and untreated groups showed no significant difference at any time point. Systemic treatment with AN-7 had a significant inhibitory effect on chemical burn-induced corneal NV in mice. These results suggest that AN-7 should be further evaluated for its therapeutic potential for the treatment of corneal NV.

A randomized clinical trial to evaluate the usefulness of amniotic membrane transplantation in bacterial keratitis healing

PurposeTo determine whether early amniotic membrane transplantation improves the outcomes among patients with bacterial keratitis. Patients and methodsIn this prospective randomized clinical trial 49 eyes from 49 patients with bacterial keratitis received routine antibiotic therapy followed by double-layer amniotic membrane transplantation during 2–5 days after start up of the medications and the second group of 50 eyes from 50 patients only received routine antibacterial therapy. The main outcomes including visual acuity, corneal healing time, scar size, hypopyon size and duration as well as the depth of corneal opacity and neovascularization were followed for a six months period. In addition, Langerhans cells density and tectonic procedures were documented during the healing period. ResultsOur results indicated statistically significant better best corrected visual acuity (p < 0.001), uncorrected visual acuity (p < 0.001), as well as contact lens corrected visual acuity (p < 0.001) at six months in the case group compared to control group. Corneal healing time, the depth of corneal opacity, hypopyon size and duration were not significantly different in the case group while the scar size (p < 0.001) was significantly smaller. Also significantly less corneal vascularization at six months (p < 0.001) and Langerhans cells density (p < 0.001) at one month were observed in the case group. ConclusionThe early use of amniotic membrane transplantation in treatment of patients with bacterial keratitis was associated with better outcomes compared to antibiotic therapy alone. More comparative studies to investigate the probable side effects as well as the cost benefit of this method are needed.

Contralateral Autologous Corneal Transplantation Experience in Mexico City

The aim of this study is to expand the limited knowledge regarding autologous contralateral penetrating keratoplasty. We report the retrospective outcomes of patients who received autokeratoplasty and contralateral opaque corneas in the donor eye at a tertiary care ophthalmology hospital in Mexico City. Eleven patients received autokeratoplasty and contralateral opaque corneas in the donor eye at our center from 2010 to 2015. The mean patient age at the time of surgery was 58 years (range, 35-85 yrs), with 4 female and 7 male patients. There were no surgical or immediate postsurgical complications in the autokeratoplasty eye. However, 1 patient had expulsive hemorrhage in the sightless eye. Follow-up duration ranged from 11 to 65 months (mean, 26 mo). During follow-up, 3 of the autokeratoplasty procedures failed because of endothelial attenuation. Identified known risk factors for failure of the eye with visual potential included the presence of an Ahmed glaucoma drainage device in 7/11 patients (63%), history of glaucoma in 8/11 (72%), past heterologous penetrating keratoplasty in 2/11 (18%), Vogt-Koyanagi-Harada syndrome in 1/11 (9%), and 4-quadrant corneal vascularization in 1/11 (9%). Autokeratoplasty is a good choice in cases having high risk factors and when fresh corneal tissue is not available. This is the largest study describing outcomes of patients who underwent autokeratoplasty. This technique offers no risk of immune rejection and no need for immunosuppression treatment. This study reports a good prognosis in cases having high risk factors for failure.

AAV vector-meditated expression of HLA-G reduces injury-induced corneal vascularization, immune cell infiltration, and fibrosis

AAV vector-meditated expression of HLA-G reduces injury-induced corneal vascularization, immune cell infiltration, and fibrosis

Preliminary results from the comparison of simple limbal epithelial transplantation with conjunctival limbal autologous transplantation in severe unilateral chronic ocular burns.

Purpose:To compare the safety, efficacy, and clinical outcomes of simple limbal epithelial transplantation (SLET) with conjunctival-limbal autologous transplantation (CLAU) in severe unilateral ocular chemical burns.Materials and Methods:Twenty patients of unilateral chronic ocular burns with more than 270° limbal stem cell deficiency and a healthy fellow eye were divided into two groups – ten patients of Group A underwent SLET while ten patients of Group B were operated for CLAU. Patients were followed up for 6 months and assessed for a stable epithelialized ocular surface, extent of reduction in vascularization and forniceal reconstruction, improvement in corneal clarity and visual acuity.Results:A stable epithelialized corneal surface was obtained in all patients, with a significant reduction in the mean clock hours of vascularization in both the groups (P < 0.001). The mean symblepharon score showed a statistically significant reduction from 1.80 ± 1.14 to 0.30 ± 0.63 in Group A and 1.70 ± 1.06 to 0.15 ± 0.24 in Group B at 6 months. Corneal clarity, as well as best-corrected visual acuity, showed a statistically significant improvement in both the groups.Conclusion:Both the procedures, SLET and CLAU, were equally effective in achieving a stable ocular surface, forniceal reconstruction, and regression of corneal vascularization. The requirement of minimal donor tissue in SLET makes it a preferred option over CLAU in cases of uniocular chronic ocular burns.

Limbal stem cell and oral mucosal epithelial transplantation from ex vivo cultivation in LSCD-induced rabbits: histology and immunologic study of the transplant epithelial sheet.

To evaluate the results of cultivated limbal epithelial and oral mucosal epithelial transplantation (CLET and COMET) in limbal stem cell deficiency (LSCD)-induced rabbit model. Six New Zealand white rabbits were divided into two groups of three rabbits each. Limbal tissue was harvested from the first group, and oral mucosal biopsy was obtained from the second group. The tissues were cultured using an explant technique with amniotic membrane as a substrate and co-culture with the 3T3 fibroblast and air-lifting method. The right eye of each rabbit was induced to have LSCD using alkali burns. After three weeks, the LSCD-induced rabbit eyes were transplanted with the cultivated limbal and oral mucosal epithelial sheet in the first and second group, respectively. The transplanted eye was evaluated weekly post-operation. After 2 months, all transplanted eyes were enucleated and the epithelial morphology and phenotype of ocular surfaces were studied and compared with normal corneal and oral mucosal tissue. At 2-month post-transplantation, the eyes of four animals recovered with corneal transparency, one partially recovered, and one failed. The histology of the majority of transplanted eyes was stratified layers of corneal epithelia similar to normal rabbit cornea with some different findings such as goblet cells in the limbal region. Corneal epithelial thickening and stromal vascularization in two animals were observed. Phenotypic characterization of transplanted eyes showed a similar pattern of marker expression with the absence of p63 expression in the limbal or corneal epithelium in the COMET group. The histology and phenotype of transplanted eyes after CLET and COMET were most likely to have similar characteristics as a normal healthy rabbit eye even though the COMET eyes have some inferior characteristics to the CLET eyes.

Allogeneic Mesenchymal Stem Cell Transplantation in Dogs With Keratoconjunctivitis Sicca.

Keratoconjunctivitis sicca (KCS) is a dysfunction in tear production associated with clinical signs, which include conjunctival hyperemia, ocular discharge, discomfort, pain, and, eventually, corneal vascularization and pigmentation. Immunosuppressive drugs are routinely administrated for long periods to treat KCS but with side effects and limited results. Evaluation of the clinical benefits of intralacrimal transplantation of allogeneic mesenchymal stem cells (MSCs) in dogs with mild-moderate and severe KCS was done. A total of 24 eyes with KCS from 15 dogs of different breeds were enrolled in the present study. A single transplantation of MSCs (1 × 106) directly into lacrimal glands (dorsal and third eyelid) was performed. The Schirmer tear tests (STTs) and ocular surface improvements were used to assess short- and long-term effects of these cells. The STTs were carried out on day 0 (before MSCs transplantation) and on days 7, 14, 21, and 28, as well as 6 and 12 months after MSC transplantation. Our data demonstrate that allogeneic MSC transplantation in KCS dogs is safe since no adverse effects were observed immediately after transplantation and in short- and long-term follow-ups. A statistically significant increase in the STT and ocular surface improvements was found in all eyes studied. In all the eyes with mild-moderate KCS, STT values reverted to those of healthy eyes, while in eyes with severe KCS, although complete reversion was not found, there was improvement in tear production and in other clinical signs. Our study shows that a single dose of a low number of MSCs can be used to treat KCS in dogs. In contrast to immunosuppressive drug use, MSC transplantation has an effect over a long period (up to 12 months), even after a single administration, and does not require daily drug administration.

Topical cyclosporine‐A in dry eye associated with chronic graft versus host disease

SummaryGraft‐versus‐host disease (GVHD) is a major complication of bone marrow transplantation and seen in 50–70% of cases. It is a complex clinical disease with many organ and system involvement. Acute form is seen in the first 3 months after transplantation, mainly as hepatitis and chronic form is mostly seen after acute GVHD. Ocular manifestations can be classifed as anterior and posterior findings but dry eye syndrome is the most frequent ocular finding and seen in 40–90% of patients with chronic GVHD. Corneal vascularization, keratitis and perforation can be seen. Topical cyclosporine‐A might be an effective and safe treatment option in dry eye related to chronic GVHD in combination with topical steroids, autologous serum, lubricant eye drops and ointments.

Corneal neovascularization: clinical aspects and the role of the immune system

SummaryRecent scientific evidences emphasized the role of corneal emo‐lymphangiogenesis and the active role of the immune system in corneal neovasculariziation (CN).Corneal neovasculariziation has an incidence rate of approx.. 1.4 million patients per year. CN is a natural defense of the cornea in the attempt to respond to invading agents, However, this process may cause permant damage to the corneal transparency and may be responsible of loss of visual function. A delicate balance regulates this ‘corneal angiogenic privilege’ between FGF and VEGF and several antiangiogenic factors (namely the role of intact epithelium, the limbus, and other antiangiogenic molecules) This paper will review the role of corneal inflammatory vascularization as well as the role of antiangiogenic factors and the involvement of the immune system in this process. New and emerging treatment to counteract the corneal neovessels will be highlighted.

Ocular tolerance in rabbits of intracameral administration of MYDRANE, a fixed combination of tropicamide, phenylephrine, and lidocaine for cataract surgery

PurposePreclinical studies have been done to evaluate the ocular tolerance of MYDRANE (tropicamide 0.02%, phenylephrine 0.31% and lidocaïne 1%) after a single intracameral (IC) injection in rabbits.Methods60 pigmented rabbits were divided in 3 groups of 10 animals by injection volume (100 or 200 μl of MYDRANE or 0.9% NaCl). One group injected with MYDRANE and the group injected with NaCl had their anterior chamber rinsed with NaCl, 1 min after IC injection. This wash was not performed for the second MYDRANE‐group in order to extend the presence of the product in the anterior chamber well beyond what is expected in clinical use. Animals were held in observation for 7 days. The following evaluations were performed: general tolerance, slit‐lamp observations, laser flare, cornea thickness, cell density of the corneal endothelium, electroretinography. After euthanasia, eyes were sampled for histology.ResultsMYDRANE was very well tolerated with or without rinsing. Very slight conjunctival effects were observed for 3 or 4 animals from groups after 200 μl‐injection and very slight corneal vascularization was observed for one animal from NaCl‐group. Inflammation in the anterior chamber was mainly observed in the eyes who were rinsed and this inflammation decreased in the course of time. Iris, fundus and lens were normal, except for 4 animals in whom a needle impact was observed on the lens, probably due to rinsing. In addition, whatever the group, cornea thickness, endothelium cell density, electroretinography parameters and ocular histology were not affected.ConclusionsFollowing IC injection of 100 or 200 μl of MYDRANE, which is the maximal injectable volume in rabbits, the ocular tolerance of MYDRANE was very good for 7 days and the ocular effects observed were attributed mainly to the method of injection and to the rinsing.

Biomaterials: Impact on Keratoprosthesis Implantation

Purpose of Review The increasing demand for corneal tissue and clinical circumstances of severe corneal scarring and vascularization have stimulated a continued interest in developing an artificial cornea from innovative biomaterials. We review the latest findings on the variety of materials used for artificial corneas and keratoprostheses, focusing most heavily on the Boston keratoprosthesis, the AlphaCor, and the Osteo-odonto Keratoprosthesis.

Safety Profile of Stromal Hydration of Clear Corneal Incisions with Cefuroxime in the Mouse Model.

The use of sutureless clear corneal incisions (CCIs) for phacoemulsification is an established surgical technique, but the dynamic morphology of the wound and poor construction can lead to an increased risk of postoperative endophthalmitis. Stromal hydration with balanced salt solution (BSS) can improve the self-sealing status. Intracameral cefuroxime has reduced endophthalmitis rates. This study investigates the safety profile of stromal hydration with cefuroxime, as sequestering antibiotic at the wound may potentially provide added protection against infection. MF-1 mice underwent bilateral CCI, followed by stromal hydration with 5 μL of 10 mg/mL cefuroxime, cefuroxime-texas red conjugate (for detection using confocal microscopy), or BSS. Corneas were harvested from 1 h to 12 weeks postoperatively; gross morphology, histology, and apoptotic cell death levels were investigated to determine the safety profile. Bactericidal activity of cefuroxime was assayed using homogenized whole cornea following stromal hydration at 1 h, 24 h, and day 7 against gram-negative Escherichia coli. Cefuroxime stromal hydration did not alter corneal morphology, with no evidence of corneal scarring or vascularization. Corneal histology and levels of apoptosis were minimal and comparable to the BSS groups up to 12 weeks. Confocal microscopy detected cefuroxime-texas red up to 1 week surrounding the corneal wound. Whole corneal tissue homogenates displayed bactericidal activity up to 24 h postoperatively. Stromal hydration of CCI with cefuroxime is safe in mouse corneas. A reservoir of antibiotic at the wound can potentially act as a barrier of defense against infection following cataract and associated ocular surgery.

Fine-Needle Diathermy with Simultaneous Subconjunctival Bevacizumab

ABSTRACTPurpose: To describe our experience of the use of subconjunctival bevacizumab in conjunction with fine-needle diathermy for the treatment of corneal vascularization. Methods: Retrospective analysis of cases treated between 2010 and 2013. Results: Those patients with corneal lipid deposition had good results following treatment with 3/5 cases requiring more than one session of treatment. A single patient with severe atopy and multiple previous failed penetrating keratoplasty underwent five sessions of treatment but his third graft subsequently also failed. Conclusion: Concurrent use of subconjunctival bevacizumab with FND gives good results in patients with lipid deposition; however, the management of cases with ongoing inflammatory processes is much more challenging.

Wholemount imaging reveals abnormalities of the aqueous outflow pathway and corneal vascularity in Foxc1 and Bmp4 heterozygous mice

Mutations in the FOXC1/Foxc1 gene in humans and mice and Bmp4 in mice are associated with congenital anterior segment dysgenesis (ASD) and the development of the aqueous outflow structures throughout the limbus. The aim of this study was to advance our understanding of anterior segment abnormalities in mouse models of ASD using a 3-D imaging approach. Holistic imaging information combined with quantitative measurements were carried out on PECAM-1 stained individual components of the aqueous outflow vessels and corneal vasculature of Foxc1+/− on the C57BL/6Jx129 and ICR backgrounds, Bmp4+/− ICR mice, and wildtype mice from each background. In both wildtype and heterozygotes, singular, bifurcated and plexus forms of Schlemm's canal were noted. Of note, missing portions of the canal were seen in the heterozygous groups but not in wildtype animals. In general, we found the number of collector channels to be reduced in both heterozygotes. Lastly, we found a significant increase in the complexity of the corneal arcades and their penetration into the cornea in heterozygotes as compared with wild types. In conclusion, our 3-D imaging studies have revealed a more complex arrangement of both the aqueous vessels and corneal arcades in Foxc1+/− and Bmp4+/− heterozygotes, and further advance our understanding of how such abnormalities could impact on IOP and the aetiology of glaucoma.

Indications and outcomes of keratoplasties in children during a 40-year period.

To report the indications and the outcomes of keratoplasties in children over four decades. A retrospective cohort study of patients aged 16years or younger who underwent keratoplasty in the Helsinki University Eye Hospital during 1968-2011. Diagnosis, preoperative status, age at the time of surgery, surgical technique, complications and follow-up time were registered. Main outcome measures were visual acuity and graft survival as assessed by Kaplan-Meier analysis. The independent role of risk factors on outcomes was evaluated by Cox multivariate regression analysis. Forty-eight keratoplasties, 42 penetrating and six lamellar, were performed in 44 eyes of 39 children at the age of 4.5months to 16years (median, 12years). Five patients had bilateral grafts, and five grafts were regrafts. The indication for keratoplasty was injury for 13 grafts, non-traumatic acquired corneal opacities for 11, keratoconus for eight, corneal dystrophy for seven, congenital corneal opacities for six and aniridia for three grafts. The cumulative proportion of clear grafts was 46% at 5years postoperatively, and the median follow-up time of clear grafts was 5.1years (range, 0.4-29years) for 41 penetrating allografts (PKP). Simultaneous intraocular surgery at the time of grafting [hazard ratio (HR) 9.7], corneal vascularization (HR 8.1) and regrafting (HR 5.4) were the main independent risk factors for graft failure in this PKP cohort. The cumulative proportion of clear grafts was 84% at 5years in the absence of any of these risk factors. PKP for keratoconus and corneal dystrophy yielded clear grafts in 83% of the eyes, and a visual acuity ≥0.3 (Snellen) in 75% of the eyes. Seventeen of the 20 graft failures were due to rejection. Favourable graft survival was obtained in primary keratoplasties for non-vascularized corneal opacities performed without any other simultaneous intraocular surgery. Visual outcome was favourable in keratoconus and corneal dystrophies and poor in most eyes with injury.

Ocular Manifestations of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Children

To describe the acute and chronic ocular manifestations of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN Overlap syndrome (Overlap syndrome) in children. Retrospective case series. Medical records of children admitted to the Hospital for Sick Children between 2001 and 2011 with SJS, TEN, and Overlap syndrome were reviewed. Demographic information, all abnormal ophthalmic findings (and median time to first diagnosis), visual acuities, and ophthalmic treatments prescribed were collected for each eye for every patient. Thirty-six children were identified for inclusion in the study. Twenty-nine (81%) had acute ocular involvement, including all patients with TEN (n= 7). Conjunctivitis was the most common (78%) clinical sign. This, together with conjunctival membranes and subconjunctival hemorrhage, were the earliest signs, presenting by a median of 1day. The percentage of patients and median time to occurrence of complications were as follows: for lid margin ulceration and corneal epithelial defects, 25%, 3days; conjunctival ulceration, 39%, 3.5days; symblepharon, 28%, 4weeks; corneal opacification, 11%, 4months; limbal stem cell failure, 8%, 7months; and corneal vascularisation, 8%, 10months after admission. Over 90% of children maintain a visual acuity of 20/40 or better in each eye at a mean follow-up of 1.4 years. Ocular involvement in SJS, TEN, and Overlap syndrome is common and the ocular manifestations may develop many months after the initial presentation, mandating the need for long-term follow-up of these children. Despite the high frequency of sight-threatening disease, most children maintain good vision in the long term.

Optical coherence tomography angiography and indocyanine green angiography for corneal vascularisation

Background/AimTo describe an optical coherence tomography angiography (OCTA) system adapted for anterior segment imaging, compared with indocyanine green angiography (ICGA) in eyes with corneal vascularisation.MethodsRetrospective study of subjects with corneal...

Outcomes of femtosecond laser-assisted mushroom-configuration keratoplasty in advanced keratoconus

To evaluate the long-term outcomes after femtosecond laser (FSL)-assisted mushroom-configuration keratoplasty in advanced keratoconus. Thirteen eyes with Amsler-Krumeich stage IV keratoconus underwent FSL-assisted mushroom-configuration penetrating keratoplasty (PKP) and deep anterior lamellar keratoplasty (DALK) at a tertiary referral centre. Preoperative risk factors included low orneal thickness, high keratometry measurements, previous hydrops, and central stromal scarring. Main outcome measures were visual acuity and refractive outcome. The median follow-up was 33 months (range: 4-43). Preoperatively, the mean corrected distance visual acuity (CDVA) was 1.22±0.47 LogMAR (range: 0.5-1.9 LogMAR), mean minimum corneal thickness was 282±100.8 μm (range: 147-478 μm), and mean average keratometric (K) value was 63.4±7.63 dioptre (D; range: 57.0-75.7 D). Four patients underwent PKP and nine underwent DALK (two converted to PKP). Five patients subsequently underwent a modified arcuate mushroom interface dissection (AMID) procedure for astigmatic correction. At the final follow-up, the mean CDVA was 0.05±0.13 LogMAR (range: -0.10 to 0.20 LogMAR), mean spherical equivalent was -3.21±3.21D, mean cylindrical refractive error was 3.23±2.20 D, and mean average K was 43.1±1.53 D. Complications included early graft dehiscence, corneal vascularisation, stromal rejection, and sclerokeratitis. Sutures were completely removed at the mean 18.4 months for PKP and 9.1 months for DALK postoperatively. FSL-assisted mushroom-configuration keratoplasty is feasible and safe in patients with stage IV keratoconus. AMID could further enhance the refractive outcome safely.

Intracorneal stromal hemorrhage in dogs and its associations with ocular and systemic disease: 39 cases.

To describe clinical features of dogs diagnosed with stromal intracorneal hemorrhage (ICH). Retrospective case series of 39 dogs (44 eyes) with ICH. Medical records of dogs evaluated by the Cornell University ophthalmology service were searched to identify animals with a clinical diagnosis of ICH between 2005 and 2014. Signalment and clinical details, including concurrent ocular disease, concurrent systemic disease, diagnostic tests performed, outcome of hemorrhage, presenting client complaint, and treatment, were recorded. Intracorneal hemorrhage was identified in 44 eyes of 39 dogs. The mean (±standard deviation) age of dogs was 11.5 years (±2.8 years). The Bichon Frise breed and older dogs were statistically over-represented relative to the entire ophthalmology service canine referral population during the same time period. Concurrent ocular disease was present in 40 eyes (91%) and included keratoconjunctivitis sicca, cataracts, and corneal ulcers. Twenty-three dogs (59%) suffered from concurrent systemic disease, most frequently diabetes mellitus, hyperadrenocorticism, hypothyroidism, and systemic hypertension. Less commonly, life-threatening systemic conditions were identified in dogs with ICH including immune-mediated hemolytic anemia, immune-mediated thrombocytopenia, metastatic neoplasia, and sepsis. Intracorneal hemorrhage was found in all corneal locations, and corneal vascularization was present in each affected eye. Intracorneal hemorrhage is an uncommon condition in dogs that occurs in association with corneal vascularization. The risk of ICH may be increased due to certain ocular and systemic diseases. Although uncommon, ICH may also be an ocular manifestation of severe immune-mediated, infectious, and neoplastic systemic diseases in dogs.