Improved Corneal Clarity after Lamellar Keratectomy (PDF) - Veterinary Ophthalmology - 2024

Received: 22 September 2023 | Revised: 12 April 2024 | Accepted: 17 April 2024 DOI: 10.1111/vop.13223 CASE REPORT Improved corneal clarity following lamellar keratectomy for corneal lipidosis in a canine...

Received: 22 September 2023 | Revised: 12 April 2024 | Accepted: 17 April 2024 DOI: 10.1111/vop.13223 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 | Christopher M. Reilly2 1 Eye Care for Animals, Chicago, Illinois, USA Abstract 2 SpecialtyVETPATH, Seattle, Objective: To report the corneal clarity outcome following lamellar keratectomy Washington, USA of arcus lipoides corneae secondary to canine hypothyroidism and report a unique Correspondence retinal manifestation of systemic disease. Alex P. Schenk, 1501 S Belcher Rd, Animal Studied: Four-­year-­old spayed female Sheepdog-­Poodle canine. Largo, FL 33771, USA. Procedure: Lamellar keratectomy OD. Email: [email protected] and [email protected] 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 aqueous, ocular hemorrhage, lipemia retinalis, and bul- lous retinal detachments.1,2,5–10 Hypothyroidism is the most common endocrinopathy ob- Crystalline corneal opacities are a common abnormal- served in dogs with an estimated prevalence of 0.2%–0.8% ity in canines. Although the appearance of these lesions of the total population.1–3 Many of these cases are the re- may be similar, the composition of the opacities may vary sult of primary acquired thyroiditis, although congenital from calcium deposits, bacterial colonies, to lipid.11,12 and secondary causes of hypothyroidism have also been Corneal lipidosis represents nonspecific lipid deposition reported.1–5 This condition creates a spectrum of systemic with subtypes including lipid keratopathy, corneal arcus, clinical signs as well as ocular manifestations such as and arcus lipoides corneae.6,11–13 In particular, arcus lipoi- keratoconjunctivitis sicca, arcus lipoides corneae, lipemic des corneae, characterized by bilateral peripheral corneal © 2024 American College of Veterinary Ophthalmologists. Veterinary Ophthalmology. 2024;27:571–576.  wileyonlinelibrary.com/journal/vop | 571  | 14635224, 2024, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/vop.13223 by Robin Stanley - National Health And Medical Research Council , Wiley Online Library on [05/01/2025]. 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 572    SCHENK et al. lipid deposits with concurrent hyperlipidemia, has been informed consent for treatment at all stages of intervention documented in association with hypothyroidism.11,13 and provided consent for publication. Severe opacification of the cornea results in significant On initial presentation, the menace responses, pupil- visual impairment. Surgical intervention to improve the lary light reflexes, and dazzle reflexes, as well as cranial visual axis is indicated with severe opacification; however, nerve examination were unremarkable oculus uterque risk of recurrent corneal opacification is unknown and (OU). Visual impairment was suspected due to corneal reports of long-­term corneal clarity outcomes following opacification and hesitant environmental navigation. lamellar keratectomy are lacking.11 Evaluation of the anterior segment revealed marked, dif- The following report documents the clinical and diag- fuse, heterogenous, white-­tan, vascularized, corneal leu- nostic findings of a canine patient with multiple ocular komas comprising 90% oculus dexter (OD) and 80% oculus manifestations of hypothyroidism. Additionally, we report sinister (OS) of the anterior stromal surface area with an the corneal clarity outcome following lamellar keratec- axial and perilimbal region of clear cornea consistent with tomy for the treatment of arcus lipoides corneae. arcus lipoides corneae (Figure 1). Examination of the fun- dus was limited by the corneal opacity with no abnormal- ities noted. The patient had a body condition score of 7/9 2 | C A S E S UMMARY with no other external systemic abnormalities. Quantitative tear testing (Schirmer Tear Test – 1), A 4-­ year-­old spayed female Sheepdog-­ poodle mix rebound tonometry (iCare TONOVET), and corneal presented for visual impairment secondary to corneal fluorescein staining were performed serially through- opacification. The progressive corneal opacification and out follow-­up visits and remained within a physiologic visual impairment had developed over the 2 years prior range throughout all time points (Appendices S1 and to referral. The patient had an unremarkable systemic S2). Complete blood count and serum biochemistry medical history aside from a vestibular episode a month performed at the initial visit revealed hyperlipidemia prior to presentation which was empirically treated characterized by hypercholesterolemia and hyper- with otic medications auris sinistra. The owner provided triglyceridemia. 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, 2024, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/vop.13223 by Robin Stanley - National Health And Medical Research Council , Wiley Online Library on [05/01/2025]. 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.    573 revealed a mild, normocytic, hyperchromic, nonregen- of atracurium besylate (10 mg/mL injectable solution, erative anemia. Fecal parasitology, heartworm antigen, Pfizer; 0.1 mg/kg IV) was administered. Ehrlichia canis, and Anaplasma phagocytophilum/platys The lamellar keratectomy was initiated using a 6400 antigen tests were negative. The patient was started on Beaver blade circumferentially starting ~1 mm from the ketorolac (0.5% ophthalmic solution, Micro Labs USA limbus to a depth estimated to be less than 50% of the Inc.; 1 drop OU q12h) and cyclosporine (Optimmune total corneal thickness. Lamellar dissection was contin- 0.2% ophthalmic ointment, Merck Animal Health; ¼ ued with a Martinez corneal dissector. A small island inch strip OU q12h). of clear cornea axially was delineated from the rest of The examination 2 months following the initial presen- the keratectomy and spared from resection. A minor de- tation revealed subjectively static corneal opacification; gree of residual opacity was noted at this time. A layer however, multifocal, circular low-­ lying, serous bullous of amnion membrane (Amnion-­Chorion Ocular Disc, retinal detachments of size ranging from ~0.2 to 1.0 ONH Vetrix) was applied to the entire surface of the cornea diameter were distributed throughout the tapetal fundus and secured with simple interrupted cardinal sutures OU (Figure 2). The optic nerve head and nontapetal fun- of 9–0 PGA (V549G, Ethicon) at the limbus. A bandage dus were subjectively normal. contact lens (PureVision, Bausch & Lomb Inc.) and a With the advent of the fundic lesions, additional diag- partial temporary tarsorrhaphy using 5–0 polypropylene nostic testing was performed. Infectious disease screen- (Prolene, Ethicon) in a horizontal mattress pattern were ing consisting of urine Blastomyces dermatitidis antigen placed. testing, Erhlichia canis, Borrelia burgdorferi, Rickettsia The excised superficial cornea OD was submitted for rickettsii, Histoplasma capsulatum, Blastomyces derma- histopathology which revealed severe, chronic granulo- titidis, Aspergillus fumigatus, and Coccidioides immitis matous keratitis with abundant intralesional cholesterol antibody titers were negative. Oscillometric blood pres- clefts, regionally extensive stromal fibrosis, and epithelial sure measurement was normal with a systolic pressure hyperplasia, consistent with granulomatous keratitis with of 120 mmHg, diastolic of 79 mmHg, and a mean arterial intralesional cholesterol. Small lymphocytes, foamy mac- pressure of 88 mmHg. Complete thyroid testing revealed rophages, and thin-­walled blood vessels were scattered a serially low total T4, low total T3, low free T4, normal throughout the tissue (Figure 3). free T3, normal T3/T4 autoantibodies, elevated TSH, and Throughout the immediate postoperative period, elevated thyroglobulin auto-­antibody. Genetic screening ketorolac and cyclosporine were discontinued OD but using a commercial genetic testing kit (Wisdom Panel, maintained OS. Ofloxacin (0.3% ophthalmic solution, Kinship Partners Inc.) revealed no abnormal copies of the Altair Pharmaceuticals Inc.; 1 drop OD q6h) and to- canine multifocal retinopathy genes (CMR 1, 2, and 3). bramycin (0.3% ophthalmic solution, Bausch & Lomb Screening for progressive retinal atrophy via the CNGB-­1 Inc.; 1 drop OD q6h), topical amnion suspension (EyeQ gene included in the testing panel was inconclusive, Amnion ophthalmic suspension, Vetrix; 1 drop OD q8h), though clinical signs were not consistent with progressive and topical lubrication (I-­Drop Vet Gel 0.3% ophthal- retinal atrophy. Serial monitoring showed no progression mic lubricant, I-­Med Animal Health; 1 drop OU q6h) of retinal lesions and visual reflexes/responses were main- were started along with carprofen (Rimadyl, Zoetis; tained. The owner elected to pursue unilateral lamellar 2.2 mg/kg PO q12h for 10 days) and gabapentin (Amneal keratectomy for the more severely affected OD and con- Pharmaceuticals LLC; 10 mg/kg PO q8h PRN). In ret- tinue monitoring the fundic lesions. rospect, the combined use of ofloxacin and tobramycin The patient was premedicated with buprenorphine without clinical, cytologic, or microbiological evidence (Buprenex 0.3 mg/mL injectable solution, Reckitt of infection was unjustified. At the 1-­week postoperative Benckiser; 0.01 mg/kg IV) and midazolam (5 mg/mL recheck, the amnion disc was intact, and the bandage injectable solution, Sun Pharmaceutical Industries; contact lens was retained. At the 2-­week postoperative 0.2 mg/kg IV) and induced with alfaxalone (10 mg/mL recheck, the tarsorrhaphy sutures were removed. No flu- injectable solution, Jurox Inc.; 2 mg/kg IV given to ef- orescein stain retention was noted, confirming epitheli- fect). Anesthesia was maintained with inhalant isoflu- alization of the corneal surface. rane (Covetrus; 1–5%) delivered via endotracheal tube. Within 1 month following surgery, the owners re- Intravenous Lactated Ringers Solution (Vetivex, Dechra; ported the patient displayed increased confidence while IV 5 mL/kg/h continuously) was administered through- navigating its environment and fewer collisions with out the procedure. The right periocular fur was clipped, objects. A moderate degree of keratitis, fibrosis, and cor- the periorbita aseptically prepped with 0.1% iodine neal pigment was noted OD throughout the immediate solution, and the patient was placed in dorsal recum- postoperative period. The degree of corneal opacifica- bency under an operating microscope. A single dose tion reduced dramatically leaving only a mild degree  | 14635224, 2024, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/vop.13223 by Robin Stanley - National Health And Medical Research Council , Wiley Online Library on [05/01/2025]. 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 574    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 atherosclerosis affects less than 0.5% of dogs due to the in- 13 months after surgery. The multifocal retinal detach- creased proportion of HDL in dogs relative to humans.10,13 ments had resolved leaving subtle circular regions of Atherosclerosis has been reported in patients with chronic altered tapetal reflectivity and color. Ketorolac was dis- hypercholesterolemia and is most often associated with continued OD and maintained once daily OS, and cyclo- hypothyroidism.2,10 The origin of the multifocal bul- sporine was maintained. lous retinal detachments is unclear but may represent Corneal opacity with vascularization OS remained sta- chorioretinal hypertension from local atherosclerosis. ble throughout the follow-­up period. The owners had ini- Alternative explanations for the retinal detachments in- tially planned to proceed with unilateral surgery for the clude infectious chorioretinitis and systemic hyperten- more severely affected OD with subsequent surgery OS. sion, although the lack of concurrent uveitis and negative Surgery OS has not been pursued as focus on continued infectious disease testing make these etiologies less likely.2 systemic health care has taken priority, the patient was A single oscillometric blood pressure measurement was not exhibiting signs of discomfort, and the patient's vi- normal, however, this does not rule out hypertensive cho- sual function was sufficient for normal navigation of its roidopathy as an etiologic cause in this case. According environment. to Gang and colleagues, oscillometry yields significantly Thyroxine supplementation (Thyro-­ tabs, LLOYD lower blood pressure readings compared to ultrasonic Inc.; 0.6 mg PO q24h) was started by the primary vet- Doppler measurements in similar anatomic sites.15 An erinarian 1 month following surgery with a notable ACVIM consensus statement suggests that measurements improvement in overall energy level noted by the own- less than 160 mmHg are repeated every 6 months, which ers shortly after. Serial T4 and serum chemistry testing was not performed in the present case.16 The absence of confirmed normal levels of thyroxine and resolution of hemorrhage and resolution of the retinal lesions without hyperlipidemia. the use of systemic antihypertensives would suggest that primary systemic hypertension is unlikely in this case. Initial medical management using topical therapy with 3 | DI S C USSION a calcineurin inhibitor (cyclosporine) and a nonsteroi- dal anti-­inflammatory (ketorolac) was chosen due to the In the present report, a canine patient with compromised prominent vascular keratitis; however, corneal opacifi- visual function secondary to severe corneal lipidosis ex- cation did not improve. Thyroxine supplementation was perienced improved corneal clarity and visual function delayed until after surgical intervention at the discretion following lamellar keratectomy. The patient's presenting of the referring veterinarian. It is unlikely that earlier in- clinical signs of lethargy, later development of sponta- tervention with supplementation would have facilitated neous retinal lesions consistent with multifocal bullous resolution of the corneal opacities given that no improve- retinal detachments, and biochemical evidence of hyper- ment was noted in the lipidosis in the contralateral eye lipidemia improved after diagnosis of hypothyroidism and despite ongoing therapy. supplementation with thyroxine. Surgical intervention has been proposed as a treatment With sustained hyperlipidemia, lipids may be mod- option to improve corneal clarity with risks of incomplete ified and deposited in the peripheral tissues including resolution or relapse of opacification.11 To the authors' the cornea (corneal lipidosis) and blood vessels (athero- knowledge, the literature is lacking reports of corneal clar- sclerosis).10,13,14 Although a common finding in humans, ity outcomes following keratectomy for corneal lipidosis. In  | 14635224, 2024, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/vop.13223 by Robin Stanley - National Health And Medical Research Council , Wiley Online Library on [05/01/2025]. 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.    575 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 lamel- lar 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 asso- ciated systemic condition for which medical treatment was possible. In patients without an identifiable, treatable cause of corneal lipidosis, the chances of recurrent corneal lipido- sis 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; for- mal 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 as- sistance 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, 2024, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/vop.13223 by Robin Stanley - National Health And Medical Research Council , Wiley Online Library on [05/01/2025]. 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 576    SCHENK et al. BC, et al., eds. Veterinary Ophthalmology. Wiley-­Blackwell; ORCID 2021:1082-1172. Alex P. Schenk https://orcid.org/0000-0002-5149-2602 12. Dubielzig RR, Ketring KL, McLellan GJ, et al. Veterinary Ocular Pathology: A Comparative Review. Saunders-­Elsevier; 2010:472. REFERENCES 13. Crispin SM. Ocular manifestations of hyperlipoproteinaemia. J 1. Scott-­ Moncrieff JC. 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