Pre-iridal Fibrovascular Membranes Research Articles

Prevalence of pre-iridal monocellular and fibrovascular membranes in canine globes affected with congenital glaucoma associated with anterior segment dysgenesis, primary glaucoma associated with goniodysgenesis, and secondary glaucoma.

The objectives of this study were to (i) evaluate the prevalence of pre-iridal monocellular and fibrovascular membranes in canine globes affected with congenital glaucoma associated with anterior segment dysgenesis (ASD), primary glaucoma associated with goniodysgenesis (GD), and secondary glaucoma, and (ii) examine the associations between monocellular and fibrovascular membranes by breed, gender, age and histopathologic ocular changes on light microscopic examination. Records of dogs who had eyes enucleated due to blindness and uncontrolled glaucoma were reviewed. Glaucoma was categorized clinically and histologically into three groups: congenital/ASD, primary/GD, and secondary glaucoma. The presence or absence and type of pre-iridal membrane (monocellular or fibrovascular) and other intraocular histologic findings were reviewed and compared statistically for each group. In total, 108 canine globes (101 dogs) were included. Pre-iridal monocellular membranes were identified with light microscopy in 10 out of 19 congenital/ASD, 29 out of 40 primary, and 23 out of 49 secondary glaucoma globes. Fibrovascular membranes were observed in 3 out of 19 congenital/ASD, 9 out of 40 in primary, and 24 out of 49 secondary glaucoma globes. There were no associations between the type of membrane and breed, gender, or age. Peripheral anterior synechiae were more common in globes with fibrovascular membranes, and uveal atrophy was more common in globes with monocellular membranes. Pre-iridal monocellular membranes are common in all types of canine glaucoma. They are identified with light microscopy most easily in cases of primary glaucoma, and they are masked by pre-iridal fibrovascular membranes in other forms of glaucoma.

Ocular porcupine quilling in dogs: Gross, clinical and histopathologic findings in 17 cases (1986-2018).

The objectives of this retrospective study were to evaluate the histopathologic changes associated with porcupine ocular quill injuries in dogs, to discuss the various methods of quill detection when quills are not grossly visible, and to discuss the pathogenesis of delayed ocular quill injuries in dogs. Seventeen globes sustaining ocular quilling injuries from 17 dogs (1986-2018) were identified in the COPLOW archives and the gross and histologic changes tabulated and compared. All cases were dogs, with one whole globe submitted from each patient. Sixteen of 17 cases had known or suspected porcupine encounters in the weeks or years preceding enucleation. Histopathologic findings included retinal detachment, hyphema, cataract, granulomatous to pyogranulomatous inflammation (uveitis, endophthalmitis, panophthalmitis), lens capsule rupture, suppurative phakitis, scleral perforation, stromal keratitis, breaks in Descemet's membrane, preiridal fibrovascular membrane, anterior and posterior synechia, Schnabel's cavernous atrophy, and periorbital fibrosis. Quill-associated ocular trauma can have a significant deleterious effect on vision and result in enucleation. The time from initial quilling to the manifestation of ocular signs may be prolonged (weeks to years). Any dog presenting for ocular signs with a history of a previous porcupine encounter should be carefully checked for quill migration into the globe as the source of ocular disease. Quills may not be visible grossly, and ancillary imaging techniques can be utilized with various rates of success.

A retrospective histologic study of 140 cases of clinically significant equine ocular disorders.

Ocular diseases are an important category in equine medicine; however, most articles regarding histologic ocular lesions in horses are exclusive to a specific condition and do not provide a complete review of clinically significant ocular disease frequency in a diagnostic laboratory. We reviewed sections of equine eyes from 140 cases (98 enucleations [biopsies] and 42 autopsies) with clinically relevant ocular alterations at 2 diagnostic centers in the United States. The most common primary conditions were non-traumatic keratitis (36), equine recurrent uveitis (ERU; 31), traumatic injuries (22), ocular and periocular neoplasms (19), and uveitis and/or endophthalmitis resulting from sepsis (18). Congenital anomalies (3) and retinal atrophy and detachment alone (3) were infrequent. Non-traumatic keratitis was frequently accompanied by anterior uveitis (22), corneal rupture (16), pre-iridal fibrovascular membrane formation (13), and secondary mycotic infection (11). ERU was the second and third most prevalent disease in autopsies and enucleations, respectively. This condition was commonly associated with glaucoma (15). Glaucoma (25) and cataract (20) were the most prevalent secondary alterations in the evaluated cases. Keratitis (20) and corneal rupture (16) were among the most prevalent consequences of trauma. Information presented herein may guide clinicians and pathologists, contributing to the early diagnosis of potentially vision-impairing conditions and raising the chances of successful treatment and cure.

Causes of Feline Uveitis: A Retrospective Study of 96 Cases at the Faculty of Veterinary Medicine Bucharest, 2012-2015

Uveitis is a common cause of blindness in feline patients as incorrectly treated or its chronicization can lead to formation of pre-iridal fibrovascular membranes, pupillary block and secondary glaucoma. The objective of this study was to investigate the causes of uveitis in cats diagnosed at the Faculty of Veterinary Medicine, Bucharest between 2012 and 2015. Medical records were reviewed and cats were considered if complete diagnostic work-up, clinical examination and imaging studies were performed. All the feline cases were serologically tested for at least two of the common infectious causes: feline leukemia virus, feline immunodeficiency virus, feline coronavirus, Toxoplasma gondii, and Bartonella spp. Ninety-six cats with a mean age of 5.42 years, ranging from 1 month to 17 years old, with a male to female ratio of 1.33/1 were diagnosed with uveitis. The European domestic cat was overrepresented at 76% followed by Birman cat (6.3%), Persian cat (4.2%), Russian blue (4.2%), Norwegian cat (2%), British Short Hair (1%), Sphynx (1%) and Cornish Rex (1%). Infectious diseases were the cause of uveitis in 31 cases (32.3%), neoplasia was diagnosed in 22 cases (22.9%), uveitis secondary to septic keratitis in 8 cases (8.3%) and uveitis secondary to direct ocular trauma in 6 cases (6.3%). Twenty-nine cats (30.2%) with a mean age of 4.33 years old were diagnosed with idiopathic or immune-mediated uveitis, less than previously reported. Aqueous flare occurred in 91 cats and keratic precipitates were noted in 39 cats. The most common infectious cause of uveitis in this study was Toxoplasma gondii (n=18). Infectious diseases remain the most common cause of feline uveitis, therefore systemic evaluation and serological investigations should be performed in all cats with uveitis, cataract and glaucoma.

Major breed distribution of canine patients enucleated or eviscerated due to glaucoma following routine cataract surgery as well as common histopathologic findings within enucleated globes

To identify the most significantly represented breeds that were enucleated or eviscerated due to intractable glaucoma following elective cataract surgery and to describe the major histopathologic features of enucleated globes. A retrospective review of the Comparative Ocular Pathology Laboratory of Wisconsin database revealed 153 canine evisceration or enucleation submissions that met inclusion criteria. The most commonly represented breeds were identified, and enucleated globes of these breeds were further evaluated histologically (n=69). Following standard hematoxylin & eosin staining, globes were evaluated for the presence of; corneal pathology, goniodysgenesis, pigment dispersion, pre-iridal fibrovascular membranes (PIFVMs), peripheral anterior, and/or posterior synechiation, inflammatory infiltrates, lens pathology, retinal pathology, and/or endophthalmitis. The most significantly represented breeds were the Cocker Spaniel (11.7%), Boston Terrier (10.5%), Labrador Retriever (6.5%), Bichon Frise (6.5%), Shih Tzu (5.8%), and Jack Russell Terrier (5.8%). Common histopathologic findings included inflammatory keratitis, the presence of PIFVMs, and lymphoplasmacytic uveal infiltrates. The Cocker Spaniel, Boston Terrier, Labrador Retriever, Bichon Frise, Shih Tzu, and Jack Russell Terrier may be at increased risk of the development of glaucoma following elective cataract surgery. These findings have potential clinical implications.

Glaucoma associated with uveal cysts and goniodysgenesis in American Bulldogs: a case series

We present a series of three American Bulldogs with clinical signs of glaucoma and intraocular inflammation accompanied by bilateral uveal cysts and abnormal gonioscopic findings. All dogs proved refractory to medical management and were enucleated. Histopathologic findings were similar in all three and included significant preiridal fibrovascular membranes and mononuclear inflammatory infiltrates in the anterior uvea. On microscopic evaluation, cysts appeared to arise primarily from the ciliary body and iridociliary sulcus, with smaller cysts also budding from the posterior iris. Pigment dispersion was variable but consistent, involving deposition of a small number of pigment-laden cells in the dependent trabecular meshwork. Cataract formation was not noted. Glaucoma associated with uveal cysts has been described previously in Golden Retrievers and Great Danes, although clinical and histopathologic findings in those breeds are not identical to those described here. American Bulldogs with uveal cysts should have gonioscopy performed and should be monitored carefully for signs of increased intraocular pressure and intraocular inflammation. Furthermore, documentation of cyst-associated glaucoma in a third breed suggests clinicians should exercise caution in dismissing uveal cysts in dogs as incidental findings.

Histopathological and Immunohistochemical Features of Vitreoretinopathy in Shih Tzu Dogs

Fifty cases of Shih Tzu ocular vitreoretinopathy were selected from the database of the Comparative Ocular Pathology Laboratory of Wisconsin. Cases with severe coexisting conditions (e.g. corneal disease, uveitis or endophthalmitis) were excluded. Microscopical changes were evaluated and immunohistochemistry was used to define spindle cells, gliosis and the presence of basement membranes in the vitreous. Expression of glial fibrillary acidic protein, vimentin and smooth muscle actin was also performed. The mean age of the 50 cases was 10.1 years (range 2.5-15 years). The most characteristic microscopical abnormalities (50/50 cases) were retinal detachment and extensive retinal tear. Additionally, extracellular, eosinophilic matrix material admixed with few spindle cells, and pre-iridal fibrovascular membrane, goniodysgenesis, secondary glaucoma, hypermature and subcapsular cataract were detected. The spindle cells within the collagen matrix were strongly labelled for expression of vimentin, with weaker expression of smooth muscle actin.

Histopathologic evaluation of the anterior segment of eyes enucleated due to glaucoma secondary to primary lens displacement in 13 canine globes

PURPOSE To describe histologic anterior segment changes in eyes affected with primary lens displacement (PLD) and secondary glaucoma. METHODS Histologic sections stained with H&E from canine eyes enucleated because of PLD and secondary glaucoma were examined. RESULTS Thirteen eyes from 12 patients were evaluated. Four dogs were castrated males and eight spayed females. Median age was 8 years of age (range 3-13). Breeds included seven terriers and five other breeds. All eyes examined demonstrated varying degrees of inflammation involving the iris and cleft. Mononuclear and melanophagic infiltration of the cleft was found in all specimens. Four globes also showed polymorphonuclear infiltrate. Pre-iridal fibrovascular membranes were clearly identified in 10 of 13 eyes. Total inflammatory score was significantly greater in all globes examined compared with an age-matched group of normal dogs. The posterior pigmented iris epithelium demonstrated a consistent pattern of hyperplasia and/or hypertrophy and cystic degeneration, more prominent in the more central regions. In some cases, hyperplasia was of greatest severity in the mid-iris and associated with thinning or flattening of the pupillary region. CONCLUSIONS These results suggest that lens instability may be associated with chronic inflammation and secondary glaucoma. Mechanical irritation from an unstable lens may result in hypertrophy and/or hyperplasia of the posterior pigmented iris epithelium and subsequent cellular exfoliation and release of melanin. An inflammatory reaction directly or indirectly related to melanin release may obstruct the outflow pathways ultimately leading to glaucoma and loss of vision. Use of topical steroids may be warranted in dogs with PLD.

Expression of vascular endothelial growth factor receptor‐1 and ‐2 in normal and diseased canine eyes

To immunohistochemically evaluate expression of vascular endothelial growth factor receptor-1 (VEGFR1) and -2 (VEGFR2) in ocular tissue of healthy dogs and dogs affected with primary glaucoma, uveitic glaucoma, and intraocular neoplasia. Enucleated globes from five dogs with primary glaucoma, five dogs with uveitic glaucoma, six dogs with intraocular neoplasms and three ophthalmically normal control dogs. Ocular tissues were obtained from enucleated globes of clinical cases or immediately following euthanasia for control dogs. Tissue sections were stained immunohistochemically for VEGFR1 and VEGFR2 via standard techniques and vascular tissue was qualitatively evaluated. Vascular endothelial VEGFR1 and VEGFR2 expression patterns are reported for normal and diseased ocular tissues. In addition, VEGFR1 and VEGFR2 expression patterns are reported for all normal ocular tissues. A constitutive expression pattern was detected for VEGFR1 by ocular vascular endothelial cells as well as nonvascular cells in the cornea, uvea, lens, and retina. VEGFR2 demonstrated limited expression in normal ocular tissue, but was widely expressed in vascular endothelium of diseased eyes, particularly in pre-iridal fibrovascular membranes. The results of this study suggest a role for VEGF receptors in both physiologic and pathologic angiogenesis in canine ocular tissue. Manipulation of this pathway may be a rational consideration for therapeutic intervention in canine ocular disease exhibiting pathologic neovascularization.

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.

Canine pre-iridal fibrovascular membranes: morphologic and immunohistochemical investigations

Pathologic intraocular neovascularization is a key component of many canine ophthalmic diseases such as uveitis, retinal detachment, intraocular neoplasms, and corneal perforation. The purpose of this study was to evaluate the structure of pre-iridal fibrovascular membranes (PIFMs) associated with several different disease processes and to identify specific factors associated with their development in the canine eye. This study examined 36 enucleated canine eyes with the diagnosis of PIFM and one of the following: lens-induced uveitis, retinal detachment, iridociliary adenoma, corneal perforation, severe hyphema, or vitreal gliovascular membranes (canine ocular gliovascular syndrome, COGS). Three histologic stains and six immunohistochemical stains were performed in all 36 PIFM eyes and four histologically normal eyes, including: hematoxylin and eosin, alcian blue periodic acid schiff (PAS), Masson's trichrome, platelet endothelial cell adhesion molecule-1 (CD31), smooth muscle actin, vimentin, laminin, vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2). Pre-iridal fibrovascular membrane extracellular matrix staining was consistent with collagen and mucins in all cases and positive for laminin in most cases. All PIFMs contained CD31-positive vessels and predominantly lymphoplasmacytic inflammation. Both PIFM vessels and spindle cells were positive for laminin, vimentin, smooth muscle actin, VEGF, and COX-2. Secondary intraocular pathology and immunohistochemical staining of other intraocular structures are also reported. Pre-iridal fibrovascular membrane morphology and immunohistochemical characteristics were similar across six canine disease processes, suggesting analogous pathophysiologic mechanisms. COX-2 and VEGF were identified using immunohistochemistry and may play a role in PIFM development.

Canine ocular onchocerciasis in the United States: two new cases and a review of the literature

Since 1991, 53 cases of canine ocular onchocerciasis have been reported in the literature worldwide, 43 of these were from Greece, five from Hungary, and five from the western United States. Information on the histopathologic features of canine ocular onchocerciasis is limited. We describe the histopathologic features of canine ocular onchocerciasis in two dogs from California that presented clinically with firm episcleral nodules and uveitis unilaterally. Pertinent literature and pathogenesis are reviewed; recognizable clinical features and treatment are discussed. The cases presented were diagnosed via histopathology of the enucleated globes and episcleral granulomas at the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW). Positive identification of adult Onchocerca within episcleral granulomas was made based on light-microscopy features. Histopathologic examination of both globes revealed episcleral parasites surrounded by granulomas containing few to moderate numbers of eosinophils. Other sequelae, in both cases, included lymphoplasmacytic uveitis, preiridal fibrovascular membranes, peripheral anterior synechiae, retinal degeneration, and optic nerve head cupping. Both male and female worms were present, as were in utero microfilariae in both cases. Worms in both cases were tentatively identified as Onchocerca lienalis. Ocular onchocerciasis should be a differential consideration in cases of canine conjunctival nodules or periorbital swelling, particularly in dogs from the western United States.

A morphologic study of intravitreal membranes associated with intraocular hemorrhage in the dog.

Abstract We aimed to characterize intravitreal membranes in dogs and determine, if possible, associated predisposing conditions. Five globes in which intravitreal membranes were identified were evaluated. These originated from four Labrador Retrievers or Labrador-cross dogs and a Springer Spaniel. The ages of the dogs ranged from 4 to 11 years. Standard histology and immunohistochemical procedures for factor VIII-related antigen, smooth muscle actin (SMA), vimentin and glial fibrillary acidic protein (GFAP) were performed. Intravitreal membranes varied from loosely to highly organized. The extent of organization corresponded with increasing immunoreactivity for vimentin and GFAP, indicating their predominantly glial origin. They were never immunopositive for smooth muscle actin, nor were they vascularized. In all cases, they were associated with intravitreal hemorrhage. Additional common findings included epiretinal membranes, retinal neovascularization, preiridal fibrovascular membranes and glaucoma. Intravitreal membranes may be a sequelae of intravitreal hemorrhage. This in turn, may arise from new vessels associated with epiretinal or preiridial membranes, or hemorrhage associated with optic disc cupping or retinal neovascularization. All of these phenomena may accompany glaucoma.

A study of the morphology of canine eyes enucleated or eviscerated due to complications following phacoemulsification.

This study was undertaken to describe the histopathologic abnormalities observed in canine eyes enucleated or eviscerated due to complications following phacoemulsification; to correlate these findings with the clinical abnormalities reported, and to suggest, if apparent, likely causes and effects of these abnormalities. Sixty-six canine globes or evisceration samples received for histopathologic interpretation over a 10-year period (1990-2000) were studied. All globes and evisceration samples were obtained from clinical patients examined by board-certified ophthalmologists. Hematoxylin and eosin (H&E) and alcian blue/periodic acid Schiff (PAS) stained sections were examined by light microscopy in every case. A tissue Gram stain was used when indicated. Clinical information obtained from the pathology submission form was reviewed in all cases, and obtained from questionnaires completed and returned by an ophthalmologist for 51 cases (77%). The most frequent histopathologic diagnoses were glaucoma (76%) and retinal detachment (64%). The most frequently reported clinical abnormalities in this series were glaucoma (86%) and uveitis (82%). Five problem areas were identified that appear to make a significant contribution to the failure of canine cataract surgery and merit further investigation: pre-iridal fibrovascular membranes; lens fiber regrowth; lens epithelial membranes; endophthalmitis, and the health of the corneal surgical incision.

Multiple ciliary body cysts and secondary glaucoma in the Great Dane: a report of nine cases.

Between 1989 and 1995 nine Great Danes were presented to the small animal clinic of the University of Zurich Teaching Hospital with glaucoma and multiple cysts in the anterior and posterior chamber. In four of the nine dogs cysts were present in both eyes; however, bilateral glaucoma was seen in one case only. Mean intraocular pressure (IOP) at initial presentation was 42 mmHg measured by applanation tonometry. With the exception of one dog, all animals were treated medically for a minimum of 13 days. Two animals were subsequently lost to follow up. Two dogs underwent evisceration with implantation of a silicone prosthesis. The glaucomatous globe was enucleated in three dogs. One owner declined surgery and the dog remained buphthalmic with a poorly controlled IOP. One animal remained visual after trans-scleral diode laser cyclophotocoagulation. Histopathology of the three enucleated globes showed multiple cysts originating from the ciliary body epithelium. The mechanism of IOP elevation is probably by anterior displacement of the iris with narrowing of the angle and collapse of the ciliary cleft. A delicate pre-iridal fibrovascular membrane was also seen in each case, which could have also contributed to the elevation of IOP. The high odds ratio of 2.23 (CI 95% 1.14, 3.99) for glaucoma and 37.01 (CI 95% 16.42, 77.81) for ciliary body cysts suggests they are both inherited in this breed. Pedigree analysis of the affected dogs failed to definitely reveal the mode of inheritance.

A histopathological study of iridociliary cysts and glaucoma in Golden Retrievers.

This is a retrospective histopathological study of archive slides from the Comparative Ocular Pathology Laboratory of Wisconsin from 1981 to 1997. Reports on eyes or ocular contents from 2176 dogs were reviewed. Five-hundred and thirty out of 2176 (24%) of the cases had a clinical or histologic diagnosis of glaucoma. Twenty-five out of 530 (5%) of the canine cases of glaucoma were in Golden Retrievers. Thirteen out of 25 (52%) of the Golden Retriever cases of glaucoma had iridociliary cysts. Iridociliary cysts in Golden Retrievers may lead to the development of glaucoma. Histologically all 13 of the cases of glaucoma and iridociliary cysts had large thin-walled cysts lined with attenuated cuboidal epithelium filling most of the posterior chamber. The following histologic features were also present: thick walled cysts containing hyaluronic acid (8/13; 62%), a solid cellular proliferation (2/13; 15%), a retrocorneal membrane associated with a defect in Descemet's membrane (7/13; 54%), iris bombé (5/13; 38%), a preiridal fibrovascular membrane (4/13; 31%), hemorrhage (4/13; 31%), a cellular membrane on the anterior lens surface (6/13; 46%), retinal detachment (5/13; 38%), peripheral anterior synechia (5/13; 38%), and posterior synechia (6/13; 46%). Complete follow up was obtained on 11/13 (85%) of the Golden Retrievers with glaucoma and iridociliary cysts. Two/11 (18%) of the dogs were euthanized due to intractable glaucoma. Eight/13 (62%) of the dogs had problems in the other eye. The other eye was diagnosed with uveitis 5/11 (45%), glaucoma 2/11(18%), pigment in the anterior chamber 3/11 (27%), and iridociliary cysts 4/11 (36%).

The Pathogenesis and Significance of Pre-iridal Fibrovascular Membrane in Domestic Animals

Histologic examination was made of 1,419 globes from domestic animals (964 dogs, 374 cats, 41 horses, and 40 cattle) with ocular disease; pre-iridal membranes (rubeosis iridis) were found in 98. The membranes originated as endothelial budding from the anterior iridal stroma and seemed to mature into fibrous or fibrovascular membranes that were often followed by hyphema or, occasionally, glaucoma. Pre-existent disease in the 98 affected globes included chronic endophthalmitis (27/98), chronic glaucoma (24/98), anterior uveal melanoma (15/98), ciliary body adenoma (14/98), neoplasms metastatic to the eye (8/98), and chronic retinal detachment (6/98). In terms of likelihood of occurrence, pre-iridal membranes seen in 21% (6/21) of globes with retinal detachment, 19% (14/75) of those with ciliary body adenomas, 14% (24/167) of those with chronic glaucoma, and 10% (15/158) of those with anterior uveal melanoma. They were detected with greatest relative frequency in horses (9/41) followed by dogs (83/964), cats (5/374) and cattle (1/40). These membranes, which are rarely detected by clinical examination, probably form in response to angiogenic factors released by ischemic retina, by neoplasms, or by leukocytes involved in ocular inflammation.