Clinicopathologic profiles of canine ocular melanosis: A comparative study between cairn terriers and non-cairn terriers.

OBJECTIVES: To identify canine breeds at risk for ocular melanosis and to compare the clinical and histologic features between affected Cairn Terriers (CTs) and non-Cairn Terriers (NCTs). DESIGN: Relative risk (RR) analysis and retrospective cohort study of dogs histologically diagnosed with ocular melanosis. PROCEDURES: The COPLOW archive was searched for globe submissions diagnosed with ocular melanosis. Six hundred fifty globes were included, and RR analysis was performed to identify at-risk NCT breeds. A cohort of 360 CT and NCT globes diagnosed from 2013 to 2023 were included in the retrospective cohort study. Clinical data were collected from submission forms, medical records, and follow-up surveys. One hundred fifty-seven submissions underwent masked histologic review. Immunohistochemical staining for CD204 was performed to determine the predominance of melanophages in affected uvea from five NCTs. RESULTS: At-risk NCT breeds included the Boxer, Labrador Retriever, and French Bulldog. Glaucoma was the reported reason for enucleation in 79.4% of submissions. At enucleation, clinical features less prevalent in NCTs than CTs included pigmentary abnormalities in the contralateral eye (33.7% vs. 63.1%, p = .0008) and abnormal episcleral/scleral pigmentation in the enucleated globe (25.4% vs. 53.6%, p = .0008). Histologic involvement of the episclera was also less frequent in NCTs than in CTs (39.7% vs. 76.9%, p = .008). Concurrent melanocytic neoplasms arising in melanosis were more common in NCTs (24.4%) than CTs (3.9%). Melanophages were not predominant in any samples evaluated immunohistochemically. CONCLUSIONS: Several popular NCT breeds carry risk for ocular melanosis, and some clinicopathologic disease features may differ from those described in CTs.

Report of a self-resolving corneal viral papilloma in a dog.

A 10-month-old male castrated beagle dog, without prior history of ocular disease, was referred for a corneal mass of the right eye. A non-painful raised mass with frond-like projections originated from the dorsotemporal paraxial cornea of the right eye. In addition, a plaque-like conjunctival lesion and several raised, smooth masses of the eyelid were noted around the right eye. An incisional biopsy of the corneal mass and an excisional biopsy of the conjunctival mass were performed. Histopathology confirmed the clinical diagnosis of viral papilloma. Conservative management with monitoring was elected, and the lesion self-resolved 3 mo after initial appearance. Key clinical message: This case suggests that monitoring is appropriate for corneal lesions definitively diagnosed as viral papillomas, as they may be self-limiting.

Rapport d'un papillome viral cornéen auto-résolutif chez un chien. Un chien beagle mâle castré âgé de 10 mois, sans antécédent de maladie oculaire, a été envoyé pour consultation pour une masse cornéenne de l'oeil droit. Une masse surélevée non douloureuse avec des projections en forme de frondes provenait de la cornée paraxiale dorso-temporale de l'oeil droit. De plus, une lésion conjonctivale en forme de plaque et plusieurs masses surélevées et lisses de la paupière ont été notées autour de l'oeil droit. Une biopsie incisionnelle de la masse cornéenne et une biopsie excisionnelle de la masse conjonctivale ont été réalisées. L'histopathologie a confirmé le diagnostic clinique de papillome viral. Une prise en charge conservatrice avec surveillance a été choisie et la lésion s'est résolue d'elle-même 3 mois après l'apparition initiale.Message clinique clé :Ce cas suggère que la surveillance est appropriée pour les lésions cornéennes définitivement diagnostiquées comme des papillomes viraux, car elles peuvent être spontanément auto-limitantes.(Traduit par Dr Serge Messier).

Clinical description with magnetic resonance appearance of a high-grade undefined optic nerve glioma with intracranial extension.

A 4-year-old mixed-breed dog was presented for hyphema and glaucoma of the right eye. Enucleation of the right globe was carried out, and histopathology examination revealed an optic nerve glioma with incomplete surgical margins. At 8 wk after surgery, the dog had depressed mentation and a diminished pupillary light reflex of the left eye. Magnetic resonance imaging revealed an irregular, heterogeneously T2 hyperintense/T1 isointense mass in the region of the optic chiasm. Compression of the rostral thalamus was present, with effacement of the pituitary gland and involvement of the right orbit. The dog was euthanized 4.5 mo after initial presentation. An undefined glioma of the right optic nerve with extension to the diencephalon was diagnosed on necropsy. Key clinical message: Although rare, intraocular glioma is a differential diagnosis for hyphema, glaucoma, and retinal detachment. Magnetic resonance imaging should be considered in cases of intraocular neoplasia, notably in those with incomplete surgical margins of the optic nerve.

Description clinique avec aspect en résonance magnétique d'un gliome indéfini de haut grade du nerf optique avec extension intracrânienne. Un chien de race croisé âgé de 4 ans a été présenté pour un hyphéma et un glaucome de l'œil droit. Une énucléation du globe droit a été réalisée et l'examen histopathologique a révélé un gliome du nerf optique aux marges chirurgicales incomplètes. Huit semaines après la chirurgie, le chien avait une diminution du processus mental et un réflexe pupillaire à la lumière diminué de l'œil gauche. L'imagerie par résonance magnétique a révélé une masse irrégulière hétérogène hyperintense T2/T1 isointense dans la région du chiasma optique. Une compression du thalamus rostral était présente, avec effacement de l'hypophyse et atteinte de l'orbite droite. Le chien a été euthanasié 4,5 mois après la présentation initiale. Un gliome indéfini du nerf optique droit avec extension au diencéphale a été diagnostiqué à l'autopsie.Message clinique clé:Bien que rare, le gliome intraoculaire est un diagnostic différentiel pour l'hyphéma, le glaucome et le décollement de la rétine. L'imagerie par résonance magnétique doit être envisagée en cas de néoplasie intraoculaire, notamment chez ceux dont les marges chirurgicales du nerf optique sont incomplètes.(Traduit par Dr Serge Messier).

Clinical and pathologic evaluation of chorioretinal lesions in wild owl species.

OBJECTIVE: Investigate histopathology and spectral-domain optical coherence tomography (OCT) imaging of wild owls with chorioretinitis and identify any potential correlation with an infectious etiology. MATERIALS AND METHODS: Ophthalmic examination and retinal OCT imaging were performed on fifteen great horned (Strix varia) and barred (Bubo virginianus) owls (30 eyes) with chorioretinitis and five owls with normal eyes (10 eyes). Testing to investigate the presence of potential infectious diseases included a complete blood count, biochemistry, protein electrophoresis, West Nile virus (WNV) plaque reduction neutralization test, Toxoplasma gondii modified direct agglutination test, WNV RT-PCR, and Avian Influenza RT-PCR. A necropsy was performed on all owls, including ocular histopathology. RESULTS: Fundus lesions included retinal detachment (7/15 owls), depigmented lesions (12/15), pigment clumping (8/15), and retinal tear (4/15). All birds were negative for WNV and Avian Influenza on RT-PCR. Of the owls with chorioretinitis, 3/15 were seropositive for WNV and 7/15 for T. gondii. Optical coherence tomography of 25/30 affected eyes revealed outer retinal lesions (19/25 eyes), retinal detachment (16/25), and retinal tears (3/25). Histopathological examination revealed outer nuclear layer atrophy (19/30 eyes), retinal detachment (18/30), retinal tears (7/30), suprachoroidal hemorrhage (12/30), scleral rupture (3/30), and ossicle fracture (3/30). CONCLUSIONS: Although 20% of birds were seropositive for WNV and 46.6% for T. gondii, histopathologic findings supported that the posterior segment lesions in the study group were likely due to blunt ocular trauma rather than an infectious etiology. The results of OCT imaging and histopathology documented retinal changes most consistent with blunt ocular trauma.

Microphthalmia With Multiple Anterior Segment Defects in Portuguese Water Dogs.

Portuguese Water Dog breeders and veterinary ophthalmologists recognize microphthalmia with multiple congenital ocular anomalies. Fifteen Portuguese Water Dog puppies (<8 weeks of age; 8 females, 7 males) and 1 adult (5 years old; castrated male) with microphthalmia were examined. The 2 most common abnormalities were microphthalmia (31/32 eyes; 97%) and lens abnormality (congenital cataract or aphakia; 32/32 eyes; 100%). Other common histologic lesions included lack of both a ciliary cleft and trabecular meshwork (15/32 eyes; 47%) and abnormal relationship of anterior segment structures (15/32 eyes; 47%). Many of the observed lesions were similar to those described in various types of anterior segment dysgenesis in humans. Our findings define the histologic lesions in affected Portuguese Water Dogs and suggest a genetic defect that causes anterior segment malformation early in development.

Canine ocular and periocular snakebites requiring enucleation: A report of 19 cases.

PURPOSE: To describe the clinical and histopathologic features secondary to ocular and periocular snakebites in dogs requiring enucleation. METHODS: Retrospective review of patients with recorded snakebite envenomation from the archives of the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) and Texas A&M Veterinary Medical Teaching Hospital (1997-2017). The cases included in this study required witnessed snakebites to the dog by the owner, clinical signs supportive of periocular or ocular envenomation, and/or histopathologic lesions compatible with snakebites. Two groups were established: ocular bites (OB) and periocular bites (PB). RESULTS: Nineteen cases were included in the study (OB = 16/19; PB = 3/19). Dogs affected were typically older (median 8 years; range 1-18), and both sexes were equally represented. Left eyes (14/19) were more likely to sustain snake-induced trauma compared to right eyes (5/19). Fifteen breeds were identified, with terriers (9/19) commonly represented. Snakes bites occurred in six US states, with the majority of cases from Texas (7/19), California (5/19), and Arizona (4/19). Common clinical signs included facial edema, corneal ulceration, keratomalacia, uveitis, hyphema, and secondary glaucoma. All eyes demonstrated vision loss prior to enucleation. Histologically, the ocular and periocular tissues contained extensive necrosis associated with envenomation. Retinal detachment, lens capsule rupture, and intraocular hemorrhage/inflammation were commonly found. CONCLUSIONS: Snakebite envenomation is a largely necrotizing disease process that can result in profound infiltrative and destructive ocular changes presumed to be related to the proteolytic factors and necrotoxins in venom. Ocular alterations secondary to snakebites may be irreversible regardless of supportive therapy instituted.

Uveal schwannoma in a brown-eyed dog.

An eleven-year-old, female spayed Boxer dog was diagnosed with a uveal schwannoma (formerly known as the spindle cell tumor of the blue-eyed dog or SCTBED) despite having a uniformly brown iris. The patient presented to emergency for ocular discomfort, and the right globe was subsequently enucleated due to glaucoma and submitted for histopathology. Upon histopathologic evaluation, a uveal schwannoma was diagnosed and confirmed with immunohistochemical staining. Complete metastatic evaluation 1 and 6 months after initial presentation did not reveal evidence of metastasis, and the dog remains systemically healthy. This case represents a unique variant of uveal schwannoma and is relevant because although the vast majority of these tumors occur in blue-eyed dogs, clinicians should not completely rule out this tumor as a differential based on the iris color.

Four cases of iridociliary tumors in domestic rabbits (Oryctolagus Cuniculus).

Spontaneously occurring ocular neoplasia is rarely reported in rabbits. This case series presents four cases of rabbits diagnosed with iridociliary tumors, which have not been previously reported in this species. Major pathological findings include epithelial tumors affecting the anterior uvea with variable pigmentation and basement membrane formation. Follow-up information was only available for two cases, but neither showed evidence of metastasis, suggesting that the prognosis for these tumors in rabbits, as in other species, may be very good.

A high content screening approach to identify molecules neuroprotective for photoreceptor cells.

PURPOSE: Retinal degenerations are a heterogeneous group of diseases in which there is slow but progressive loss of photoreceptors (PR). There are currently no approved therapies for treating retinal degenerations. In an effort to identify novel small molecules that are (1) neuroprotective and (2) promote PR differentiation, we have developed microscale (1,536 well) cell culture assays using primary retinal neurons. METHODS: Primary murine retinal cells are isolated, seeded, treated with a 1,280 compound chemical library in a 7 point titration and then cultured under conditions developed to assay protection against an introduced stress or enhance PR differentiation. In the protection assays a chemical insult is introduced and viability assessed after 72 h using CellTiterGlo, a single-step chemiluminescent reagent. In the differentiation assay, cells are isolated from the rhodopsin-GFP knock-in mouse and PR differentiation is assessed by fixing cells after 21 days in culture and imaging with the Acumen plate-based laser cytometer (TTP Labtech) to determine number and intensity of GFP-expressing cells. Positive wells are re-imaged at higher resolution with an INCell2000 automated microscope (GE). Concentration-response curves are generated to pharmacologically profile each compound and hits identified by xx. RESULTS: We have developed PR differentiation and neuroprotection assays with a signal to background (S/B) ratios of 11 and 3, and a coefficient of variation (CV) of 20 and 9 %, suitable for chemical screening. Staurosporine has been shown in our differentiation assay to simultaneously increase the number of rhodopsin positive objects while decreasing the mean rhodopsin intensity and punctate rhodopsin fluorescent objects. CONCLUSIONS: Using primary murine retinal cells, we developed high throughput assays to identify small molecules that influence PR development and survival. By screening multiple compound concentrations, dose-response curves can be generated, and the false negative rate minimized. It is hoped that this work will identify both potential preclinical candidates as well as molecular probes that will be useful for analysis of the molecular mechanisms that promote PR differentiation and survival.

Fusarium solani species complex associated with carapace lesions and branchitis in captive American horseshoe crabs Limulus polyphemus.

Captive American horseshoe crabs Limulus polyphemus housed at the National Aquarium presented with a variety of shell and gill lesions over a 3 yr period. Carapace lesions were located on both the dorsal and ventral prosoma and opisthosoma and included multifocal circular areas of tan discoloration, ulcerations, and/or pitting lesions, extending from superficial to full thickness. Gill lesions involved both the book gill cover (operculum) and individual book gill leaflets and included multifocal circular areas of tan discoloration, tan to off-white opaque proliferative lesions, and/or areas of black discoloration. Histopathology revealed fungal hyphae, with variable morphology throughout the thickened and irregular cuticle of the carapace and occasionally penetrating into subcuticular tissues, with associated amebocytic inflammation. Book gill leaflets were infiltrated by fungal hyphae and contained necrotic debris and amebocytes. Thirty-eight of 39 animals (97%) evaluated via histopathological examination had intralesional fungal hyphae. Fungal cultures of carapace and gill lesions were attempted in 26 tissue samples from 15 individuals and were positive in 13 samples (50%), with 10 cultures (77%) yielding identification to genus. Fusarium sp. was identified in 8 of the 10 cultures (80%) via culture morphology. The Fusarium solani species complex was confirmed in 6 of these 8 (75%) via polymerase chain reaction amplification of 2 different ribosomal-specific sequences of isolated fungal DNA. Ante-mortem systemic and topical treatments were performed on some affected individuals, but no appreciable change in lesions was observed. Mycotic dermatitis and branchitis are serious health issues for captive American horseshoe crabs.

Tumor-like lymphoplasmacytic conjunctivitis in the third eyelid in a dog.

This report aims to describe a case of tumor-like lymphoplasmacytic conjunctivitis in a 7-year-old spayed-female Pomeranian. On complete ophthalmic examination, a mass with papillary projections was noted on the bulbar surface of the right third eyelid. Debulking of the mass was performed while preserving as much of the third eyelid as possible. On the histopathological examination, the mass was diagnosed as lymphoplasmacytic conjunctivitis with mild epithelial hyperplasia. Although a slight regrowth of the mass was noted 3 weeks after surgery, intralesional injection of triamcinolone acetonide led to its disappearance. There was no further recurrence after 5 months.

Development of Crystalline Corneal Opacities (Steroid Keratopathy) in Dogs After Treatment With Ophthalmic Corticosteroids.

PURPOSE: To retrospectively evaluate and describe the relationship between the use of topical corticosteroids and the development of crystalline corneal opacities (steroid keratopathy) in a colony of research Beagles and Beagle-derived dogs. METHODS: Medical records of 73 purpose-bred Beagles and Beagle-derived dogs were reviewed from June 2012 to May 2021. All dogs were treated with topical ophthalmic corticosteroids for at least 21 days. In addition to regular ophthalmic examination, some dogs also had a systemic lipid profile (n = 6) performed to work up further and characterize the crystalline corneal opacities. Globes of 3 dogs were examined histopathologically. RESULTS: Axial stromal crystalline corneal opacities were appreciated in 25 eyes of 14 dogs after a median of 141 days after initiating treatment (35-396 days). Multiple corticosteroids were used, including neomycin-polymyxin b-dexamethasone 0.1% ophthalmic ointment, prednisolone acetate 1% ophthalmic suspension, and difluprednate 0.05% ophthalmic emulsion (Durezol). Resolution of corneal opacity was documented in 4 of 25 eyes when ophthalmic corticosteroids were discontinued after a median of 406.5 days (271-416 days). Histopathologic examination revealed a dense band of acellular material, poorly staining with periodic acid-Schiff, subtending the corneal epithelium, and being surrounded by spindle cells. CONCLUSIONS: This case series documents the onset of steroid keratopathy in Beagles and Beagle-derived dogs after treatment with ophthalmic corticosteroids. Clinical resolution of steroid keratopathy lesions may be possible after discontinuation of ophthalmic corticosteroids.

Microphthalmia, aphakia and agenesis of the optic chiasm and tract in a wild fox squirrel (Sciurusniger).

We describe gross and histopathological features of multiple ocular and neuro-ophthalmic abnormalities in a fox squirrel (Sciurus niger). Ophthalmic findings included severe bilateral microphthalmos, with the right eye more affected than the left. Histopathology confirmed severe microphthalmia, aphakia, disorganized retinal tissue and small optic nerves, as well as agenesis of the optic chiasm and optic tract. This combination of neuro-ophthalmic abnormalities has not been previously described in wild animals.

Limbal Squamous Cell Carcinoma in a Black Baldy Cow: Case Report and Surgical Treatment.

Objective: To document a case of limbal squamous cell carcinoma (SCC) in an adult Black Baldy cow treated with photodynamic therapy (PDT) as an adjunctive therapy following surgical excision. Animals Studied. One privately owned 8-year-old female, entire, Black Baldy cow. Procedures. A complete ophthalmic examination was performed on an adult Black Baldy cow for assessment of a mass affecting the left eye. Following a routine partial incision superficial lamellar keratectomy and conjunctivectomy under local analgesia using a Peterson retrobulbar block, photodynamic therapy was performed as an adjunctive treatment to lower the chance for recurrence and improve the prognosis for the globe. Results: Histopathologic analysis of the limbal mass was reported to be consistent with a squamous cell carcinoma, removed with clean margins. The patient was comfortable and visual with no signs of tumor recurrence 11 months after surgery. Conclusion: Superficial lamellar keratectomy and conjunctivectomy with adjunctive photodynamic therapy is an effective treatment for limbal squamous cell carcinoma and may be performed as an alternative to enucleation, exenteration, euthanasia, or slaughtering in cattle.

What Is Your Diagnosis?

In collaboration with the American College of Veterinary Radiology.

Prolonged blockade of VEGF receptors does not damage retinal photoreceptors or ganglion cells.

It has recently been reported that relatively short-term inhibition of vascular endothelial growth factor (VEGF) signaling can cause photoreceptor cell death, a potentially clinically important finding since VEGF blockade has become an important modality of treatment of ocular neovascularization and macular edema. However, in a set of studies in which we achieved extended and complete blockage of VEGF-induced vascular leakage through retinal expression of a VEGF binding protein, we did not observe any toxicity to retinal neurons. To follow-up on these apparently discrepant findings, we designed a set of experiments with the kinase inhibitor SU4312, which blocks phosphorylation of VEGF receptors, to look directly for evidence of VEGF inhibition-related retinal toxicity. Using transgenic mice with sustained expression of VEGF in photoreceptors, we determined that periocular injection of 3 microg of SU4312 every 5 days markedly suppressed subretinal neovascularization, indicating effective blockade of VEGF signaling. Wild-type mice given periocular injections of 5 microg of SU4312 every 5 days for up to 12 weeks showed normal scotopic and photopic electroretinograms (ERGs), no TUNEL stained cells in the retina, and no reduction in outer nuclear layer thickness. Incubation of cultured ganglion cells or retinal cultures containing photoreceptors with high doses of SU4312 did not reduce cell viability. These data suggest that blocking VEGF signaling in the retina for up to 12 weeks does not damage photoreceptors nor alter ERG function and should reassure patients who are receiving frequent injections of VEGF antagonists for choroidal and retinal vascular diseases.

Comprehensive Clinical, Diagnostic, and Advanced Imaging Characterization of the Ocular Surface in Spontaneous Aqueous Deficient Dry Eye Disease in Dogs.

PURPOSE: To perform a comprehensive clinical, diagnostic, and imaging characterization of the ocular surface in West Highland White Terriers (WHWTs) diagnosed with aqueous deficient dry eye (ADDE) disease. METHODS: Six ADDE-affected and 13 ADDE-unaffected WHWT dogs were enrolled and underwent clinical assessment and disease scoring, tear osmolarity, phenol red thread test, Schirmer tear test, tear film breakup time, fluorescein staining, Rose bengal and lissamine green vital dye staining, meibometry, corneal esthesiometry, ultrasound pachymetry, optical coherence tomography, in vivo confocal microscopy, and conjunctival biopsy. Subjective assessment of their condition was provided by owner-reported surveys. RESULTS: ADDE-affected WHWT dogs had higher median clinical disease (conjunctiva: 5.75 vs. 0.00; cornea: 14.00 vs. 5.00; total: 17.50 vs. 5.00), vital staining (Rose bengal: 2.25 vs. 1.50; lissamine green: 2.00 vs. 1.00), and histologic disease (conjunctiva: 2 vs. 0) scores when compared with the controls. In addition, ADDE-affected WHWTs had significantly lower phenol red thread test (5.0 vs. 17.5, mm/15 s), Schirmer tear test (3 vs. 20, mm/min), tear film breakup time (3.6 vs. 13.9, s) values and higher area under the curve values for meibometry (394 vs. 245, meibometry units [MU]). There were no significant differences in other tear film tests performed. Advanced imaging revealed decreased tear meniscus height (optical coherence tomography) and variable pigment deposition within corneal epithelial cells (in vivo confocal microscopy). CONCLUSIONS: This comprehensive assessment of ADDE-affected WHWTs depicts the ocular surface changes associated with quantitative lacrimal gland dysfunction. Importantly, ADDE-affected WHWTs may prove a valuable naturally occurring ADDE model for investigating underlying pathophysiological mechanisms and the development of novel therapeutics.

Electroretinographic features of the retinopathy, globe enlarged (rge) chick phenotype.

PURPOSE: The purpose of the study was to characterize the electroretinographic features of the autosomal recessive retinopathy, globe enlarged (rge) phenotype, in chickens (Gallus gallus). METHODS: Dark-adapted, light-adapted intensity series and light-adapted 30 Hz flicker responses were recorded from rge and age matched normal control chicks from one to 270 days of age. Retinal sections from rge and control retinas were examined in 7 and 270-day-old chicks. RESULTS: Electroretinogram (ERG) thresholds of rge birds were raised, the intensity response plots were shifted toward brighter intensities, and retinal sensitivity was reduced. The leading slope of the dark- and light-adapted a-waves was more shallow than normal, suggesting altered photoreceptor responses. The inner retinal components to the ERG were also abnormal; there was a marked lack of oscillatory potentials and an abnormally smooth and broad shape to the b-wave. Additionally, the b-wave was supernormal in response to brighter stimuli in the earlier stages of the disease. There was a progressive deterioration in ERG amplitudes with age that mirrored a slowly progressive thinning of the photoreceptor layer. CONCLUSIONS: The rge chicken has unusual ERG changes from an early age with altered waveforms and initially they develop a supernormal b-wave. This is followed by a progressive reduction of ERG amplitudes with age. The changes suggest that both photoreceptor and inner retinal responses are abnormal. Additional studies are needed to further elucidate the origin of the abnormal ERG components in the rge chick.

Effects of prostaglandin analogs on blood flow velocity and resistance in the ophthalmic artery of rabbits.

PURPOSE: The aim of this study was to investigate the effects of prostaglandin analogs on blood flow in the ophthalmic artery of clinically healthy rabbits. METHODS: Fifty-five clinically healthy New Zealand white rabbits were divided into six groups, and the left eyes were treated for four weeks with the preservative benzalkonium chloride (BAK) only or a topical formulation of different prostaglandin analogs (bimatoprost BAK, tafluprost BAK-free, travoprost BAK, travoprost POLYQUAD, and latanoprost BAK). Color Doppler imaging was performed before and after the treatments. The mean values of the peak systolic velocity (PSV) and end diastolic velocity and the resistive index (RI) were calculated. Statistical analysis was performed to compare the differences pre- and post-treatment for each drug and post-treatment among the drugs. RESULTS: The prostaglandin analogs did not affect PSV. Bimatoprost BAK, travoprost POLYQUAD, and latanoprost BAK did not change RI. Tafluprost BAK-free and travoprost BAK therapy resulted in similar reductions in RI. No significant differences pre- and post-treatment were found when BAK was administered alone. CONCLUSION: The prostaglandin analogs tafluprost BAK-free and travoprost BAK improved blood flow in the ophthalmic artery in healthy New Zealand white rabbits, which suggests that these drugs enhance the prevention of the progression the progression of glaucoma.

Detailed histopathologic characterization of the retinopathy, globe enlarged (rge) chick phenotype.

PURPOSE: The purpose of this study was to characterize the morphological abnormalities in the retinas of chicks (Gallus gallus) suffering from the autosomal recessive disease, retinopathy, globe enlarged (rge/rge). METHODS: rge/rge affected and age matched control retinas were examined from hatch up to 730 days of age. Thickness of retinal layers at six retinal regions was measured from plastic embedded sections. Morphological features were examined on semi-thin sections by light microscopy and on ultra-thin sections by transmission electron microscopy. Immunohistochemistry was performed using a panel of several different antibodies. Additionally, comparative counting of rod outer segments, rows of cells in the inner nuclear layer, and ganglion cells per unit length was performed. RESULTS: The earliest changes observed in rge/rge retinas were disorganization of the outer plexiform layer and abnormal location of the endoplasmic reticulum of the photoreceptors. In rge/rge retinas, cone pedicles were larger, irregular in shape, and usually contained multivesicular bodies. In addition, synaptic ribbons of the cone pedicles and rod spherules in rge/rge retinas were less numerous compared to controls. Large glycogen deposits progressively accumulated in the perinuclear cytoplasm associated with the abnormally located endoplasmic reticuli in accessory cones and rods. Total retinal thickness progressively decreased with age in rge/rge birds. This was accompanied by a decrease in the number of cells in the inner nuclear layer and a decrease in the number of rod outer segments (OSs). Several changes were detected in the rge/rge retinas using immunohistochemistry, including mislocalized opsin immunoreactivity of rod photoreceptors, a decrease in number and disorganization of opsin positive rod OSs (especially in the peripheral regions), a decrease in number of tyrosine hydroxylase positive neurites in the distal inner plexiform layer, and activation of macroglial and microglial cells. CONCLUSIONS: As we previously reported, the rge/rge chick has vision loss that is not the result of photoreceptor loss and is unusual in that electroretinographic responses, although abnormal, are maintained until well after vision loss has developed. The phenotype is associated with a developmental disruption of both rod and cone photoreceptor synaptic terminals that progresses with age. It is possible that these changes may be indicative of abnormal circuitry within the outer plexiform layer, and that they underlie the progressive loss of vision in rge/rge birds. Other early changes suggesting photoreceptor abnormality are dilation of photoreceptor cell bodies, abnormal positioning of endoplasmic reticulum in the perinuclear region that is associated with abnormal glycogen deposition, and mislocalization of opsin immunoreactivity in rods. The rge/rge birds develop globe enlargement after the morphological and electroretinographic abnormalities. Globe enlargement in chicks can be induced by a number of different environmental factors. It is possible that abnormal signaling of photoreceptors to inner retinal cells could induce excessive ocular growth in the rge/rge birds. Many of the morphological changes such as retinal thinning seen in older rge/rge birds may be partly the result of the considerable globe enlargement that occurs later in the disease process. Molecular genetic studies to identify the causal gene mutation should help explain the morphological features of the rge/rge phenotype and clarify their association with vision loss and electroretinographic abnormalities.