Chemical ciliary body ablation in dogs with chronic glaucoma and anterior lens luxation: A retrospective review from 2017 to 2022.

OBJECTIVES: To evaluate the clinical outcomes of chemical ciliary body ablation (CBA) in dogs with chronic glaucoma and concurrent anterior lens luxation and to investigate adverse ocular effects of this procedure. PROCEDURES: Retrospective review of 17 dogs (18 eyes) with chronic glaucoma and concurrent anterior lens luxation treated with intravitreal gentamicin with or without dexamethasone sodium phosphate or triamcinolone acetonide. Data collected included signalment, concurrent ocular disease, topical medications prescribed, follow-up duration, and intraocular pressure (IOP) pretreatment, posttreatment, and at the last follow-up visit. Success was defined as an IOP <25 mmHg with no additional procedures or ocular hypotensive medications at the last examination to date. RESULTS: The success rate for CBA in dogs with chronic glaucoma and concurrent anterior lens luxation was 88.9% without the need of additional surgical or ocular hypotensive therapies. Glaucoma was suspected to be secondary to lens luxation in 72.2% of cases. The most common postoperative complications were phthisis bulbi (50.0%), keratoconjunctivitis sicca (27.8%), and uveitis (27.8%). Long-term management with topical nonsteroidal anti-inflammatories, corticosteroids, and/or immunomodulators was needed in 70.6% of cases. CONCLUSIONS: CBA with intravitreal injection of gentamicin is effective at maintaining an IOP <25 mmHg in dogs with chronic glaucoma and concurrent anterior lens luxation. Management of postoperative sequelae commonly requires continued use of topical medications.

Prevalence and type of ocular disease in a population of aged captive nondomestic felids.

OBJECTIVES: Report of prevalence and type of ocular disease in a captive population of nondomestic felids. METHODS: Medical records of 202 cats from 1993 to 2018 were reviewed. Species, age at diagnosis, sex, ocular examination abnormalities, systemic/physical examination abnormalities, type of examination (visual, sedated, or anesthetized), ocular structures affected, other diagnostics, therapy, and resolution of ocular disease were recorded. RESULTS: A total of 202 nondomestic felids including 18 different species (bobcat, caracal, cougar, Fishing cat, Geoffroy's cat, jaguar, jungle cat, leopard, leopard cat, liger, lion, lynx, ocelot, Sand cat, Savannah cat, serval, snow leopard, and tiger) from a rescue facility were evaluated. Forty-six ocular lesions were diagnosed in 33 (16.3%) cats from 8 different species (bobcat, caracal, cougar, leopard, lion, ocelot, serval, and tiger) with a mean age of 16 ± 5.9 years at time of diagnosis. Ocular lesions included corneal disease (37%) (ulcerations, perforations, keratitis, corneal scars), cataracts (23.9%), hyphema (8.7%), lens luxation (6.5%), retinal detachment (6.5%), uveitis (4.3%), conjunctival disease (4.3%), retinal degeneration (2.1%), glaucoma (2.1%), and optic neuritis (2.1%). Therapies included medical (topical antibiotics, anti-inflammatories, serum, etc.) and/or surgical management (enucleation, intracapsular lens extraction, corneoconjunctival transposition, and corneal burr debridement). CONCLUSIONS: To the authors' knowledge, this is the first report of the prevalence of ocular disease in a population of captive nondomestic felids. It is difficult to diagnose and treat ocular disease in nondomestic cats due to challenges related to handling, diagnostics, and therapeutics in nondomestic species. Ocular disease seen in this population is similar to that found in domestic cat populations.

Using pharmacy technicians and electronic health record capabilities to improve outcomes for patients with cardiovascular disease.

OBJECTIVE: This study aimed to compare lipid and blood pressure (BP) control before and after implementing a certified pharmacy technician (CPhT) protocol that optimized electronic health record (EHR) capabilities and shifted work from clinical pharmacy specialists (CPSs) to CPhT. SETTING: Kaiser Permanente Colorado's pharmacist-managed cardiac risk reduction service (which manages dyslipidemia, hypertension, and diabetes for all patients with atherosclerotic cardiovascular disease). PRACTICE DESCRIPTION: In 2019, a protocol that optimized EHR capabilities and allowed work to be offloaded from CPS to CPhT was implemented. Filtered views within the EHR were created that bucketed patients with specific lipid results criteria. The CPhT protocol provided guidance to CPhT on determining whether patients were at low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein (non-HDL) goals, on appropriate statin intensity, adherent to medications, and whether the most recent BP was controlled. The CPhT notified CPS of uncontrolled patients who would assess and manage these patients, as necessary. The CPhT notified controlled patients of their results. PRACTICE INNOVATION: Data on the outcomes of incorporating pharmacy technicians to support CPS clinical activities in ambulatory clinical pharmacy are limited. EVALUATION DETHODS: This retrospective study compared a "Pharmacist-Driven" (index date: January 1, 2016) with a "Tech-Enhanced" (index date: January 1, 2019) group. The primary outcome was the proportion of patients at all goals defined as LDL-C < 70 mg/dL, non-HDL < 100 mg/dL, and BP < 140/90 mm Hg at 1 year after the index dates. RESULTS: There were 6813 patients included (mean age: 70.2 ± 11.1 years, 71.4% male): 3130 and 3683 in the "Pharmacist-Driven" and "Tech-Enhanced" groups, respectively. The proportion of patients who attained LDL-C, non-HDL, and BP goals was higher in the "Tech-Enhanced" group (51.1% vs. 39.7%, P < 0.001) than the "Pharmacist-Driven" group. CONCLUSION: A protocol integrating EHR decision support and CPhTs enabled work to shift to from CPS to CPhT and improved clinical outcomes.

Pharmacologic ciliary body ablation for chronic glaucoma in dogs: A retrospective review of 108 eyes from 2013 to 2018.

OBJECTIVE: To evaluate the long-term outcome and efficacy of intravitreal injection of gentamicin and dexamethasone sodium phosphate (IVGD) or triamcinolone in end-stage glaucoma patients and determine pre-procedure prognostic indicators of success and post-operative complications. PROCEDURE: Medical records were reviewed for 108 dogs (108 eyes) treated with intravitreal gentamicin with or without dexamethasone sodium phosphate or triamcinolone for glaucoma between 2013 and 2018 with 3 months of minimum follow-up. Signalment and clinical findings, including type of glaucoma, pre-procedure intraocular pressure (IOP), chronicity, procedure protocol, and outcome were recorded. Success was defined as an intraocular pressure of ≤25 mm Hg at the time of last re-examination or no ocular hypotensive medications at 3 months or longer post-injection. RESULTS: The overall success rate for pharmacologic ablation was 95%. The success rate for dogs receiving no ocular hypotensive medications was 86%. Seventy-six eyes (70.4%) had primary glaucoma, and 32 eyes (29.6%) had secondary glaucoma. Age at the time of injection had no effect on initial success but did in final success (P =-.03) for dogs requiring repeat injections. Cocker Spaniels required the most repeat 2nd and 3rd injections (3/12 dogs) and (2/4 dogs), respectively. No preoperative variable significantly affected the success rate. The most common complications were phthisis bulbi (59.2%), corneal edema (25.9%), and ulcerative keratitis (22.3%). Uncontrolled IOP resulted in enucleation in two dogs (1.8%). CONCLUSIONS: Pharmacologic ablation has a high overall success rate in lowering IOP to ≤25 mm Hg short-term in blind, glaucomatous canine eyes. Type of glaucoma, pre-procedure IOP, chronicity, and protocol did not affect success.

Food dyes as P-glycoprotein modulators.

The drug transporter P-glycoprotein (P-gp) is often investigated in drug-interaction studies because the activity is modulated by a wide variety of xenobiotics including drugs, herbal products, and food components. In this study, we tested six common arylsulfonate food dyes-allura red, carmoisine, ponceau 4R, quinolone yellow, sunset yellow, and tartrazine-as activators and inhibitors of P-gp activity in vitro. The dyes were studied as P-gp activators by measuring ATPase activity in P-gp-expressing membranes. Compared to verapamil, a known activator of P-gp, the six food dyes showed no stimulatory activity. The potential for these six food dyes to act as P-gp inhibitors was tested in an intracellular efflux assay with P-gp-expressing cells. Compared to GF120918, a known P-gp inhibitor, there was no inhibitory activity for these six food dyes. The six food dyes tested do not interact with P-gp in vitro and, therefore, are unlikely cause clinical drug-food dye interactions. Further investigation is necessary to determine whether these food dyes could interact with other drug transporters.

A retrospective analysis of lipid-laden aqueous humor in dogs: Thirty cases.

OBJECTIVE: To describe the clinical presentation and outcome of canine patients that present with lipid-laden aqueous humor (LLA) and to evaluate its association with other ocular and systemic disorders. METHODS: Medical records were identified and reviewed of 30 dogs presenting with clinical signs of LLA between 2013 and 2017 and compared to the canine referral population during the same time period. The percentage of dogs affected by LLA and potential risk factors were compared between groups. RESULTS: There were 40 eyes in 30 dogs with LLA out of 8011 (0.4%) referrals. The mean age of dogs with LLA was significantly younger than dogs without LLA (P = .0334). Sex was not associated with LLA. Miniature Schnauzers were more likely to have LLA than mixed breeds (P < .0001). Incidence of LLA was significantly higher in eyes also affected by corneal ulceration (P = .0018) or phacoemulsification (P = .0001). Sixty-two percent and 51% of dogs with LLA had concurrent diabetes mellitus and hypertriglyceridemia, respectively. Average triglyceride level of dogs with LLA was 1087 mg/dL (±544) (reference 50-150 mg/dL) and average cholesterol level was 575 mg/dL (±232) (reference 125-300 mg/dL). Complete resolution of LLA was achieved in all dogs re-examined with an average of 20.2 days (range 4-175 days) after diagnosis. There were 6/30 dogs lost to follow-up. Recurrence of LLA occurred at least once in 4/24 dogs (16.7%) after resolution. CONCLUSIONS: Lipid-laden aqueous humor occurs more frequently in Miniature Schnauzers. Corneal ulceration and phacoemulsification are risk factors. Complete resolution was seen in all cases with a low incidence of recurrence.

Retrospective analysis of ocular neuropathies in diabetic dogs following cataract surgery.

OBJECTIVES: To describe and compare the cumulative incidence and clinical progression of ocular neuropathies in diabetic dogs vs nondiabetic dogs following cataract surgery. METHODS: Medical records of 196 diabetic and 442 nondiabetic dogs who underwent cataract surgery between 2004 and 2015 were reviewed. The percentage of patients affected by neuropathy and potential risk factors were compared between groups. RESULTS: Patients with diabetes mellitus (DM) were 20.4 times more likely to develop an ocular neuropathy than patients without DM (12.24% vs 0.68%). Twenty-four diabetic patients were affected by mononeuropathies or polyneuropathies including Horner's syndrome (n = 20), facial neuropathy (n = 5), and neurogenic keratoconjunctivitis sicca (NKCS) (n = 5). The odds of a diabetic patient developing Horner's syndrome and NKCS were 86.3 and 20.7 times higher than a nondiabetic patient, respectively. The average duration of DM prior to diagnosis of neuropathy was 659 days (range 110-2390 days; median 559 days). Complete resolution was achieved in 10 of 22 neuropathies (45%) within an average of 248 days (range 21-638 days; median 187 days) after diagnosis. CONCLUSIONS: The odds of developing an ocular neuropathy, specifically Horner's syndrome and NKCS, are statistically higher in diabetic patients compared to nondiabetic patients. Neuropathies were observed as a long-term complication in this group of diabetic patients, and complete resolution of the neuropathy was observed in less than half of the affected population.

Retinal detachment and glaucoma in the Boston Terrier and Shih Tzu following phacoemulsification (135 patients): 2000-2014.

OBJECTIVES: To report the cumulative incidence of retinal detachment (RD) and glaucoma following phacoemulsification in Boston Terriers and Shih Tzu in the southeastern United States over a 14-year period and investigate the potential predisposing risk factors. METHODS: Medical records of 83 Shih Tzu and 52 Boston Terriers that underwent phacoemulsification between 2000 and 2014, with or without intraocular lens placement, were reviewed. For a comparison population, phacoemulsification data from 45 Labrador Retrievers, 73 Schnauzers, and 159 Bichon Frises were evaluated. Information collected included signalment, concurrent systemic diseases, preoperative findings, surgical details, postoperative complications, and duration of follow-up. Percentages of patients to develop RD and glaucoma were assessed, as well as potential risk factors. Minimum of 3 months of follow-up after surgery was required for inclusion. RESULTS: Retinal detachment occurred in 7.7% (7/91 eyes) and 8.9% (11/123 eyes) and glaucoma occurred in 38.0% (35/91 eyes) and 29.3% (36/123 eyes) of Boston Terriers and Shih Tzu, respectively. Mean follow-up time was 804 days. Neither Boston Terriers nor Shih Tzu were at increased risk for RD or glaucoma when compared to the other breeds, and no significant risk factors for either breed were identified in the final multivariate analysis. CONCLUSIONS: The cumulative incidence of RD in Boston Terrier and Shih Tzu reported here was in agreement with previously reported nonbreed specific percentages (2.7-8.4%). The cumulative incidence of glaucoma in this population of Boston Terriers and Shih Tzu was higher than previously reported nonbreed specific percentages (5.1-18.8%).

Effect of an Imposed Contact on Secondary Structure in the Denatured State of Yeast Iso-1-cytochrome c.

There is considerable evidence that long-range interactions stabilize residual protein structure under denaturing conditions. However, evaluation of the effect of a specific contact on structure in the denatured state has been difficult. Iso-1-cytochrome c variants with a Lys54 → His mutation form a particularly stable His-heme loop in the denatured state, suggestive of loop-induced residual structure. We have used multidimensional nuclear magnetic resonance methods to assign 1H and 15N backbone amide and 13C backbone and side chain chemical shifts in the denatured state of iso-1-cytochrome c carrying the Lys54 → His mutation in 3 and 6 M guanidine hydrochloride and at both pH 6.4, where the His54-heme loop is formed, and pH 3.6, where the His54-heme loop is broken. Using the secondary structure propensity score, with the 6 M guanidine hydrochloride chemical shift data as a random coil reference state for data collected in 3 M guanidine hydrochloride, we found residual helical structure in the denatured state for the 60s helix and the C-terminal helix, but not in the N-terminal helix in the presence or absence of the His54-heme loop. Non-native helical structure is observed in two regions that form Ω-loops in the native state. There is more residual helical structure in the C-terminal helix at pH 6.4 when the loop is formed. Loop formation also appears to stabilize helical structure near His54, consistent with induction of helical structure observed when His-heme bonds form in heme-peptide model systems. The results are discussed in the context of the folding mechanism of cytochrome c.

The Interaction between the Third Type III Domain from Fibronectin and Anastellin Involves ß-Strand Exchange.

Anastellin is a small recombinant fragment derived from the extracellular matrix protein fibronectin; it comprises the first type III (FN3) domain without the two N-terminal ß-strands. It inhibits angiogenesis, tumor growth, and metastasis in mouse models and requires endogenous fibronectin for its in vivo anti-angiogenic activity. It binds to fibronectin in vitro and converts the soluble protein to insoluble fibrils that structurally and functionally resemble fibronectin fibrils deposited in the extracellular matrix by cells. Anastellin binds to several FN3 domains in fibronectin, but how it interacts with these domains and why the interactions lead to aggregation of fibronectin are not well understood. In this work, we investigated the interaction between anastellin and the third FN3 domain (3FN3) from fibronectin. We show that anastellin binds with high affinity to a peptide comprising the two N-terminal ß-strands from 3FN3, and we present here the structure of the resulting complex. The peptide and anastellin form a composite FN3 domain, with the two N-terminal ß-strands from 3FN3 bound in place of the two ß-strands that are missing in anastellin. We also demonstrate using disulfide cross-linking that a similar interaction involving the two N-terminal ß-strands of 3FN3 occurs when intact 3FN3 binds to anastellin. 3FN3 adopts a compact globular fold in solution, and to interact with anastellin in a manner consistent with our data, it has to open up and expose a ß-strand edge that is not accessible in the context of the folded domain.

Ophthalmic diagnostic testing and examination findings in a colony of captive brown pelicans (Pelecanus occidentalis).

OBJECTIVE: To establish reference values and report ophthalmic examination findings in a colony of captive brown pelicans (Pelecanus occidentalis). DESIGN: Descriptive study. ANIMALS STUDIED: Sixty-three captive brown pelicans in Florida were examined. PROCEDURES: A complete ophthalmic examination including Schirmer tear test (STT), applanation tonometry, fluorescein stain, biomicroscopy, and direct and indirect ophthalmoscopy was performed. A-scan ultrasonography was performed to measure axial globe length (AGL), anterior chamber depth (ACD), lens thickness, and vitreal chamber length. Fifty-two adults and 11 juvenile pelicans with an age range of 4 months to 38 years were evaluated. RESULTS: Twenty-nine pelicans (46%) had a normal ocular examination. Mean STT in normal pelicans was 5.45 ± 1.88 mm/min. Mean intraocular pressure (IOP) in normal pelicans was 10.86 ± 1.61 mmHg. One pelican was fluorescein positive unilaterally. Mean AGL was 20.70 ± 0.62 mm. Mean ACD was 3.38 ± 0.19 mm. Mean axial lens diameter (ALD) was 5.19 ± 0.23 mm. Mean vitreal chamber depth (VCD) was 12.15 ± 0.53 mm. Twenty-three pelicans (36.51%) had cataracts, 17 pelicans (26.98%) had vitreal degeneration, 18 pelicans (28.57%) had corneal disease, and seven pelicans (11.11%) had evidence of significant ocular trauma, which included collapsed anterior chamber or lens luxation. CONCLUSIONS AND CLINICAL RELEVANCE: To the author's knowledge, this is the first report of normal ophthalmic parameters and the incidence and type of ocular disease in a captive flock of brown pelicans. This information may aid in the diagnosis and treatment of brown pelicans with ocular disease.

Use of a nictitating membrane flap for treatment of feline acute corneal hydrops-21 eyes.

OBJECTIVE: To evaluate the effectiveness of the use of a nictitating membrane flap (NMF) as therapy in 19 cats (21 eyes) affected with feline acute corneal hydrops (FACH). METHODS: Medical records from 19 cats diagnosed with FACH and treated with a NMF were retrospectively evaluated. Information was collected from multiple veterinary hospitals and included signalment, medical history, therapy, and ocular outcome. RESULTS: Breeds included 13 Domestic Shorthairs, 2 Exotic Shorthairs, 2 Maine Coons, 1 Persian, and 1 Domestic Medium Hair. Two cats were bilaterally affected. Median age of cats was 3.2 years (range 0.26-15 years). Eleven patients were spayed females, 6 were neutered males, and 2 were intact males. Topical steroids were previously administered in 5 (23.8%) eyes; oral steroids were previously administered in 7 cats (36.8% of patients); three patients received both oral and topical steroids. Thirteen of 21 (61.9%) eyes had a history of ocular disease including ulcerative and nonulcerative keratitis, anterior uveitis, corneal sequestrum, conjunctivitis, and glaucoma. Median duration of NMF was 15 days (range 6-30 days). Follow-up ranged from 12 to 1601 days (median 169 days). Corneal perforation occurred in 1 (4.7%) eye and was successfully repaired. One lesion (4.7%) in a diabetic patient did not resolve. Nineteen of the treated eyes (90.5%) resolved with no complications. CONCLUSIONS: A nictitating membrane flap successfully treated 90.5% of FACH eyes (89.5% of patients).

Structure and unfolding of the third type III domain from human fibronectin.

Fibronectin is a modular extracellular matrix protein that is essential for vertebrate development. The third type III domain (3FN3) in fibronectin interacts with other parts of fibronectin and with anastellin, a protein fragment that causes fibronectin aggregation. 3FN3 opens readily both as an isolated domain in solution and when part of fibronectin in stretched fibrils, and it was proposed that this opening is important for anastellin binding. We determined the structure of 3FN3 using nuclear magnetic resonance spectroscopy, and we investigated its stability, folding, and unfolding. Similar to most other FN3 domains, 3FN3 contains two antiparallel ß-sheets that are composed of three (A, B, and E) and four (C, D, F, and G) ß-strands, respectively, and are held together by a conserved hydrophobic interface. cis-trans isomerization of P847 at the end of ß-strand C leads to observable conformational heterogeneity in 3FN3, with a cis peptide bond present in almost one-quarter of the molecules. The chemical stability of 3FN3 is relatively low, but the folding rate constant in the absence of denaturant is in the same range as those of other, more stable FN3 domains. Interestingly, the unfolding rate constant in the absence of denaturant is several orders of magnitude higher than the unfolding rate constants of other FN3 domains investigated to date. This unusually fast rate is comparable to the rate of binding of 3FN3 to anastellin at saturating anastellin concentrations, consistent with the model in which 3FN3 has to unfold to interact with anastellin.

Structural and functional characterization of the acidic region from the RIZ tumor suppressor.

RIZ (retinoblastoma protein-interacting zinc finger protein), also denoted PRDM2, is a transcriptional regulator and tumor suppressor. It was initially identified because of its ability to interact with another well-established tumor suppressor, the retinoblastoma protein (Rb). A short motif, IRCDE, in the acidic region (AR) of RIZ was reported to play an important role in the interaction with the pocket domain of Rb. The IRCDE motif is similar to a consensus Rb-binding sequence LXCXE (where X denotes any amino acid) that is found in several viral Rb-inactivating oncoproteins. To improve our understanding of the molecular basis of binding of Rb to RIZ, we investigated the interaction between purified recombinant AR and the pocket domain of Rb using nuclear magnetic resonance spectroscopy, isothermal titration calorimetry, and fluorescence anisotropy experiments. We show that AR is intrinsically disordered and that it binds the pocket domain with submicromolar affinity. We also demonstrate that the interaction between AR and the pocket domain is mediated primarily by the short stretch of residues containing the IRCDE motif and that the contribution of other parts of AR to the interaction with the pocket domain is minimal. Overall, our data provide clear evidence that RIZ is one of the few cellular proteins that can interact directly with the LXCXE-binding cleft on Rb.

The effects of intravenous romifidine on intraocular pressure in clinically normal horses and horses with incidental ophthalmic findings.

DESIGN: Original study. OBJECTIVE: To evaluate the effect of sedation with romifidine hydrochloride 1% (Sedivet: Boehringer-Ingelheim) on intraocular pressure (IOP) in the normal horse and horses with incidental ophthalmic findings as measured by applanation tonometry. ANIMALS: Nineteen clinically normal horses (13 geldings, six mares) and eight horses (three geldings, five mares) with incidental ophthalmic findings were included in this study. PROCEDURES: All horses underwent complete ophthalmic examination with pharmacologic mydriasis a minimum of 2 weeks prior to IOP evaluation. Baseline intraocular pressure values were obtained following auriculopalpebral nerve block and topical anesthetic. Immediately thereafter, romifidine was administered intravenously (75 µg/kg) and the IOP recorded at 5, 15, 30, 45 and 60 min postsedation in both eyes. Five successive readings were obtained at each time point, the low and high value discarded, and three remaining readings averaged for a mean. RESULTS: The changes with time were consistent between eyes and OD and OS results were pooled. The mean IOP at baseline was 26.35 ± 5.57 mmHg. Mean IOP values were significantly lower than baseline at 5 (P < 0.0001), 15 (P < 0.0001), 30 (P = 0.0003), 45 (P < 0.0001) and 60 (P = 0.0005) minutes. The largest change from baseline (16.7%) was noted at t = 15 min. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of romifidine significantly decreased the IOP from baseline at all time points measured. The greatest decline in IOP was noted at 15 min postsedation. Results are consistent with other studies noting a decline in IOP with administration of α-2 agonists.