Improved Corneal Clarity Following Lamellar Keratectomy for Corneal Lipidosis in a Canine (PDF)

Received: 22 September 2023 DOI: 10.1111/vop.13223 | Revised: 12 April 2024 | Accepted: 17 April 2024 CASE REPORT Improved corneal clarity following lamellar keratectomy for corneal lipidosis in a canine with ocular manifestations of hypothyroidism Alex P. Schenk1 | Annora Sheehan Gaerig1 1 Eye Care...

Received: 22 September 2023 DOI: 10.1111/vop.13223 | Revised: 12 April 2024 | Accepted: 17 April 2024 CASE REPORT Improved corneal clarity following lamellar keratectomy for corneal lipidosis in a canine with ocular manifestations of hypothyroidism Alex P. Schenk1 | Annora Sheehan Gaerig1 1 Eye Care for Animals, Chicago, Illinois, USA 2 SpecialtyVETPATH, Seattle, Washington, USA Correspondence Alex P. Schenk, 1501 S Belcher Rd, Largo, FL 33771, USA. Email: [email protected] and [email protected] | Christopher M. Reilly2 Abstract Objective: To report the corneal clarity outcome following lamellar keratectomy of arcus lipoides corneae secondary to canine hypothyroidism and report a unique retinal manifestation of systemic disease. Animal Studied: Four-­year-­old spayed female Sheepdog-­Poodle canine. Procedure: Lamellar keratectomy OD. Results: Bilateral severe arcus lipoides corneae was noted in the initial presentation. Bilateral, symmetric, and multifocal bullous retinal detachments were observed at subsequent visits. Biochemical testing revealed hyperlipidemia presumed to be associated with primary acquired thyroiditis. Corneal clarity and visual behaviors were significantly improved following unilateral lamellar keratectomy with no evidence of recurrence within the year following surgery. Bilateral retinal detachments and hyperlipidemia resolved months after initiation of thyroxine supplementation. Corneal lipidosis in the untreated eye remained static. Conclusions: Lamellar keratectomy is a viable surgical option for the treatment of arcus lipoides corneae. Hypothyroidism should be considered a differential diagnosis for spontaneous, bilateral, multifocal, and serous retinal detachments. KEYWORDS arcus lipoides corneae, bullous retinal detachment, corneal surgery, dog, endocrinopathy 1 | I N T RO DU CT ION Hypothyroidism is the most common endocrinopathy observed in dogs with an estimated prevalence of 0.2%–0.8% of the total population.1–3 Many of these cases are the result of primary acquired thyroiditis, although congenital and secondary causes of hypothyroidism have also been reported.1–5 This condition creates a spectrum of systemic clinical signs as well as ocular manifestations such as keratoconjunctivitis sicca, arcus lipoides corneae, lipemic aqueous, ocular hemorrhage, lipemia retinalis, and bullous retinal detachments.1,2,5–10 Crystalline corneal opacities are a common abnormality in canines. Although the appearance of these lesions may be similar, the composition of the opacities may vary from calcium deposits, bacterial colonies, to lipid.11,12 Corneal lipidosis represents nonspecific lipid deposition with subtypes including lipid keratopathy, corneal arcus, and arcus lipoides corneae.6,11–13 In particular, arcus lipoides corneae, characterized by bilateral peripheral corneal © 2024 American College of Veterinary Ophthalmologists. Veterinary Ophthalmology. 2024;00:1–6.  wileyonlinelibrary.com/journal/vop | 1 | SCHENK et al.    lipid deposits with concurrent hyperlipidemia, has been documented in association with hypothyroidism.11,13 Severe opacification of the cornea results in significant visual impairment. Surgical intervention to improve the visual axis is indicated with severe opacification; however, risk of recurrent corneal opacification is unknown and reports of long-­term corneal clarity outcomes following lamellar keratectomy are lacking.11 The following report documents the clinical and diagnostic findings of a canine patient with multiple ocular manifestations of hypothyroidism. Additionally, we report the corneal clarity outcome following lamellar keratectomy for the treatment of arcus lipoides corneae. 2 | C A S E S UMMARY A 4-­ year-­ old spayed female Sheepdog-­ poodle mix presented for visual impairment secondary to corneal opacification. The progressive corneal opacification and visual impairment had developed over the 2 years prior to referral. The patient had an unremarkable systemic medical history aside from a vestibular episode a month prior to presentation which was empirically treated with otic medications auris sinistra. The owner provided informed consent for treatment at all stages of intervention and provided consent for publication. On initial presentation, the menace responses, pupillary light reflexes, and dazzle reflexes, as well as cranial nerve examination were unremarkable oculus uterque (OU). Visual impairment was suspected due to corneal opacification and hesitant environmental navigation. Evaluation of the anterior segment revealed marked, diffuse, heterogenous, white-­tan, vascularized, corneal leukomas comprising 90% oculus dexter (OD) and 80% oculus sinister (OS) of the anterior stromal surface area with an axial and perilimbal region of clear cornea consistent with arcus lipoides corneae (Figure 1). Examination of the fundus was limited by the corneal opacity with no abnormalities noted. The patient had a body condition score of 7/9 with no other external systemic abnormalities. Quantitative tear testing (Schirmer Tear Test – 1), rebound tonometry (iCare TONOVET), and corneal fluorescein staining were performed serially throughout follow-­up visits and remained within a physiologic range throughout all time points (Appendices S1 and S2). Complete blood count and serum biochemistry performed at the initial visit revealed hyperlipidemia characterized by hypercholesterolemia and hypertriglyceridemia. Testing performed prior to referral F I G U R E 1 External photographs of the anterior segment of both eyes at initial and final examinations. Note the leukomatous, vascularized opacity obscuring much of the corneal surface area with a thin region of perilimbal clear cornea consistent with the lucent zone of Vogt. An exophytic eyelid margin mass is evident on the central upper eyelid OS in addition to the corneal opacity. Following lamellar keratectomy OD and eyelid wedge excision OS, significantly improved corneal clarity OD with mild fibrosis, keratitis, perilimbal pigment are noted along with no recurrence of the adnexal mass OS. (A) initial examination OD; (B) initial examination OS; (C) final examination OD; (D) final examination OS. 14635224, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/vop.13223 by Robin Stanley - National Health And Medical Research Council , Wiley Online Library on [03/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 2 revealed a mild, normocytic, hyperchromic, nonregenerative anemia. Fecal parasitology, heartworm antigen, Ehrlichia canis, and Anaplasma phagocytophilum/platys antigen tests were negative. The patient was started on ketorolac (0.5% ophthalmic solution, Micro Labs USA Inc.; 1 drop OU q12h) and cyclosporine (Optimmune 0.2% ophthalmic ointment, Merck Animal Health; ¼ inch strip OU q12h). The examination 2 months following the initial presentation revealed subjectively static corneal opacification; however, multifocal, circular low-­ lying, serous bullous retinal detachments of size ranging from ~0.2 to 1.0 ONH diameter were distributed throughout the tapetal fundus OU (Figure 2). The optic nerve head and nontapetal fundus were subjectively normal. With the advent of the fundic lesions, additional diagnostic testing was performed. Infectious disease screening consisting of urine Blastomyces dermatitidis antigen testing, Erhlichia canis, Borrelia burgdorferi, Rickettsia rickettsii, Histoplasma capsulatum, Blastomyces dermatitidis, Aspergillus fumigatus, and Coccidioides immitis antibody titers were negative. Oscillometric blood pressure measurement was normal with a systolic pressure of 120 mmHg, diastolic of 79 mmHg, and a mean arterial pressure of 88 mmHg. Complete thyroid testing revealed a serially low total T4, low total T3, low free T4, normal free T3, normal T3/T4 autoantibodies, elevated TSH, and elevated thyroglobulin auto-­antibody. Genetic screening using a commercial genetic testing kit (Wisdom Panel, Kinship Partners Inc.) revealed no abnormal copies of the canine multifocal retinopathy genes (CMR 1, 2, and 3). Screening for progressive retinal atrophy via the CNGB-­1 gene included in the testing panel was inconclusive, though clinical signs were not consistent with progressive retinal atrophy. Serial monitoring showed no progression of retinal lesions and visual reflexes/responses were maintained. The owner elected to pursue unilateral lamellar keratectomy for the more severely affected OD and continue monitoring the fundic lesions. The patient was premedicated with buprenorphine (Buprenex 0.3 mg/mL injectable solution, Reckitt Benckiser; 0.01 mg/kg IV) and midazolam (5 mg/mL injectable solution, Sun Pharmaceutical Industries; 0.2 mg/kg IV) and induced with alfaxalone (10 mg/mL injectable solution, Jurox Inc.; 2 mg/kg IV given to effect). Anesthesia was maintained with inhalant isoflurane (Covetrus; 1–5%) delivered via endotracheal tube. Intravenous Lactated Ringers Solution (Vetivex, Dechra; IV 5 mL/kg/h continuously) was administered throughout the procedure. The right periocular fur was clipped, the periorbita aseptically prepped with 0.1% iodine solution, and the patient was placed in dorsal recumbency under an operating microscope. A single dose    | 3 of atracurium besylate (10 mg/mL injectable solution, Pfizer; 0.1 mg/kg IV) was administered. The lamellar keratectomy was initiated using a 6400 Beaver blade circumferentially starting ~1 mm from the limbus to a depth estimated to be less than 50% of the total corneal thickness. Lamellar dissection was continued with a Martinez corneal dissector. A small island of clear cornea axially was delineated from the rest of the keratectomy and spared from resection. A minor degree of residual opacity was noted at this time. A layer of amnion membrane (Amnion-­Chorion Ocular Disc, Vetrix) was applied to the entire surface of the cornea and secured with simple interrupted cardinal sutures of 9–0 PGA (V549G, Ethicon) at the limbus. A bandage contact lens (PureVision, Bausch & Lomb Inc.) and a partial temporary tarsorrhaphy using 5–0 polypropylene (Prolene, Ethicon) in a horizontal mattress pattern were placed. The excised superficial cornea OD was submitted for histopathology which revealed severe, chronic granulomatous keratitis with abundant intralesional cholesterol clefts, regionally extensive stromal fibrosis, and epithelial hyperplasia, consistent with granulomatous keratitis with intralesional cholesterol. Small lymphocytes, foamy macrophages, and thin-­walled blood vessels were scattered throughout the tissue (Figure 3). Throughout the immediate postoperative period, ketorolac and cyclosporine were discontinued OD but maintained OS. Ofloxacin (0.3% ophthalmic solution, Altair Pharmaceuticals Inc.; 1 drop OD q6h) and tobramycin (0.3% ophthalmic solution, Bausch & Lomb Inc.; 1 drop OD q6h), topical amnion suspension (EyeQ Amnion ophthalmic suspension, Vetrix; 1 drop OD q8h), and topical lubrication (I-­Drop Vet Gel 0.3% ophthalmic lubricant, I-­Med Animal Health; 1 drop OU q6h) were started along with carprofen (Rimadyl, Zoetis; 2.2 mg/kg PO q12h for 10 days) and gabapentin (Amneal Pharmaceuticals LLC; 10 mg/kg PO q8h PRN). In retrospect, the combined use of ofloxacin and tobramycin without clinical, cytologic, or microbiological evidence of infection was unjustified. At the 1-­week postoperative recheck, the amnion disc was intact, and the bandage contact lens was retained. At the 2-­week postoperative recheck, the tarsorrhaphy sutures were removed. No fluorescein stain retention was noted, confirming epithelialization of the corneal surface. Within 1 month following surgery, the owners reported the patient displayed increased confidence while navigating its environment and fewer collisions with objects. A moderate degree of keratitis, fibrosis, and corneal pigment was noted OD throughout the immediate postoperative period. The degree of corneal opacification reduced dramatically leaving only a mild degree 14635224, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/vop.13223 by Robin Stanley - National Health And Medical Research Council , Wiley Online Library on [03/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License SCHENK et al. | SCHENK et al.    F I G U R E 2 Fundic images of the left eye after initial examination and the final follow-­up. Note the multifocal bullous retinal detachments throughout the tapetal fundus 1 month after the initial presentation with resolution of the detachments and subtle altered tapetal reflectivity at final examination. (A) fundus OS 1 month after initial presentation; (B) fundus OS at final examination. of fibrosis, keratitis, and pigment at the final follow-­up 13 months after surgery. The multifocal retinal detachments had resolved leaving subtle circular regions of altered tapetal reflectivity and color. Ketorolac was discontinued OD and maintained once daily OS, and cyclosporine was maintained. Corneal opacity with vascularization OS remained stable throughout the follow-­up period. The owners had initially planned to proceed with unilateral surgery for the more severely affected OD with subsequent surgery OS. Surgery OS has not been pursued as focus on continued systemic health care has taken priority, the patient was not exhibiting signs of discomfort, and the patient's visual function was sufficient for normal navigation of its environment. Thyroxine supplementation (Thyro-­ tabs, LLOYD Inc.; 0.6 mg PO q24h) was started by the primary veterinarian 1 month following surgery with a notable improvement in overall energy level noted by the owners shortly after. Serial T4 and serum chemistry testing confirmed normal levels of thyroxine and resolution of hyperlipidemia. 3 | DI S C USSION In the present report, a canine patient with compromised visual function secondary to severe corneal lipidosis experienced improved corneal clarity and visual function following lamellar keratectomy. The patient's presenting clinical signs of lethargy, later development of spontaneous retinal lesions consistent with multifocal bullous retinal detachments, and biochemical evidence of hyperlipidemia improved after diagnosis of hypothyroidism and supplementation with thyroxine. With sustained hyperlipidemia, lipids may be modified and deposited in the peripheral tissues including the cornea (corneal lipidosis) and blood vessels (atherosclerosis).10,13,14 Although a common finding in humans, atherosclerosis affects less than 0.5% of dogs due to the increased proportion of HDL in dogs relative to humans.10,13 Atherosclerosis has been reported in patients with chronic hypercholesterolemia and is most often associated with hypothyroidism.2,10 The origin of the multifocal bullous retinal detachments is unclear but may represent chorioretinal hypertension from local atherosclerosis. Alternative explanations for the retinal detachments include infectious chorioretinitis and systemic hypertension, although the lack of concurrent uveitis and negative infectious disease testing make these etiologies less likely.2 A single oscillometric blood pressure measurement was normal, however, this does not rule out hypertensive choroidopathy as an etiologic cause in this case. According to Gang and colleagues, oscillometry yields significantly lower blood pressure readings compared to ultrasonic Doppler measurements in similar anatomic sites.15 An ACVIM consensus statement suggests that measurements less than 160 mmHg are repeated every 6 months, which was not performed in the present case.16 The absence of hemorrhage and resolution of the retinal lesions without the use of systemic antihypertensives would suggest that primary systemic hypertension is unlikely in this case. Initial medical management using topical therapy with a calcineurin inhibitor (cyclosporine) and a nonsteroidal anti-­inflammatory (ketorolac) was chosen due to the prominent vascular keratitis; however, corneal opacification did not improve. Thyroxine supplementation was delayed until after surgical intervention at the discretion of the referring veterinarian. It is unlikely that earlier intervention with supplementation would have facilitated resolution of the corneal opacities given that no improvement was noted in the lipidosis in the contralateral eye despite ongoing therapy. Surgical intervention has been proposed as a treatment option to improve corneal clarity with risks of incomplete resolution or relapse of opacification.11 To the authors' knowledge, the literature is lacking reports of corneal clarity outcomes following keratectomy for corneal lipidosis. In 14635224, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/vop.13223 by Robin Stanley - National Health And Medical Research Council , Wiley Online Library on [03/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 4    | 5 F I G U R E 3 (A) H&E, ×10. Photomicrograph of the superficial cornea OD, with hyperplastic epithelium to the top. The stroma is heavily infiltrated by irregular, variably distinct clear clefts (acicular or cholesterol clefts), mixed histiocytic and lymphocytic inflammation, and thin-­walled blood vessels. (B) H&E, ×20. Photomicrograph at higher magnification. Foamy macrophages (arrowheads) and multinucleated giant cells (arrow) are scattered throughout the lipid deposits. Neovascular lumina are indicated by asterisks. (C) H&E, ×40. High magnification of macrophages surrounding cholesterol clefts (center) with scattered small lymphocytes and a few foamy macrophages (arrowhead). There is a background of small blood vessels (asterisks), and the basal corneal epithelium is at the upper right. the present report, a canine patient with compromised visual function secondary to severe corneal lipidosis experienced improved corneal clarity and visual function following lamellar keratectomy without relapse of the opacification within a year following surgery. The successful outcome in this case should be interpreted with caution. This patient had an associated systemic condition for which medical treatment was possible. In patients without an identifiable, treatable cause of corneal lipidosis, the chances of recurrent corneal lipidosis postsurgery may be higher. Reports with larger sample sizes and a wider spectrum of etiologies are indicated. AUTHOR CONTRIBUTIONS Alex P. Schenk: Conceptualization; data curation; formal analysis; writing – original draft; writing – review and editing. Annora Sheehan Gaerig: Conceptualization; data curation; supervision; writing – review and editing. Christopher M. Reilly: Data curation; writing – review and editing. ACKNOWLEDGMENTS The authors would like to thank Thomas Miller for his assistance with critical review of the manuscript. FUNDING INFORMATION The treatments and diagnostics were funded privately by the owner of the patient. CONFLICT OF INTEREST STATEMENT The authors have no conflicts of interest to declare. DATA AVAILABILITY STATEMENT Data are available upon request due to privacy/ethical restrictions. ETHICS STATEMENT The owner provided informed consent for treatment at all stages of intervention and provided consent for publication. 14635224, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/vop.13223 by Robin Stanley - National Health And Medical Research Council , Wiley Online Library on [03/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License SCHENK et al. | SCHENK et al.    ORCID Alex P. Schenk https://orcid.org/0000-0002-5149-2602 REFERENCES 1. Scott-­ Moncrieff JC. Clinical signs and concurrent diseases of hypothyroidism in dogs and cats. Vet Clin Small Anim. 2007;37:709-722. 2. Webb AA, Cullen CL. Ocular manifestations of systemic disease. In: Gelatt KN, Ben-­Shlomo G, Gilger BC, et al., eds. Veterinary Ophthalmology. Wiley-­Blackwell; 2021:2329-2420. 3. Ferguson DC. Testing for hypothyroidism in dogs. 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SUPPORTING INFORMATION Additional supporting information can be found online in the Supporting Information section at the end of this article. How to cite this article: Schenk AP, Gaerig AS, Reilly CM. Improved corneal clarity following lamellar keratectomy for corneal lipidosis in a canine with ocular manifestations of hypothyroidism. Vet Ophthalmol. 2024;00:1-6. doi:10.1111/vop.13223 14635224, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/vop.13223 by Robin Stanley - National Health And Medical Research Council , Wiley Online Library on [03/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 6