The SPOTS System: An Ocular Scoring System Optimized for Use in Modern Preclinical Drug Development and Toxicology

Eaton, Joshua Seth; Miller, Paul E.; Bentley, Ellison; Thomasy, Sara M; Murphy, Christopher J.

doi:10.1089/jop.2017.0108

Cited by 78 publications

(70 citation statements)

References 37 publications

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“…Safety of the technique and behavior of the thermogel were consistent with previous reports of SCo injections in horses and the use of copolymers in ophthalmology [10,24,[38][39][40][41]. Even though there was a significant increase in conjunctival swelling following SCo injection, a score of 2 is considered to be mild [29,30]. Swelling was most likely an enlargement within the conjunctiva due to the gel deposit, since it was restricted to the area of injection, rather than diffuse edema and inflammation.…”

Section: Discussionsupporting

confidence: 82%

“…Histological analysis alone, whenever euthanasia is the endpoint, is a valuable tool to assess tissue damage due to a drug [28]. In live animals, non-invasive, semiquantitative systems described by McDonald and Shadduck, and Hackett and McDonald are frequently cited in preclinical drug development works [29]. More specifically, slit lamp-based scoring systems are recorded using the modified Hackett-McDonald system, where clinical findings can be semiquantitatively assessed and scores used for further analysis [30].…”

Section: Introductionmentioning

confidence: 99%

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Sustained-release voriconazole-thermogel for subconjunctival injection in horses: ocular toxicity and in-vivo studies

et al. 2020

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Background: Keratomycosis is a relatively common, sight threatening condition in horses, where treatment is often prolonged and costly. Subconjunctival (SCo) injections offer less resistance to drug diffusion than the topical route, resulting in better penetration to the ocular anterior segment. Voriconazole, a second generation triazole antifungal, is effective against common fungal organisms causing keratomycosis. If combined with a thermogel biomaterial, voriconazole can be easily injected in the SCo space to provide sustained drug release. The purpose of this study was to evaluate the drug concentrations in the anterior segment and clinical effects after SCo injections of voriconazole-containing thermogel: poly (DL-lactide-co-glycolide-b-ethylene glycol-b-DL-lactide-co-glycolide) (PLGA-PEG-PLGA) in healthy equine eyes. Results: Voriconazole aqueous humor (AH) and tear concentrations were compared between 6 horses, receiving 1% voriconazole applied topically (0.2 mL, q4h) (Vori-Top) or 1.7% voriconazole-thermogel (0.3 mL) injected SCo (Vori-Gel). For the Vori-Gel group, voriconazole concentrations were measured in AH and tears at day 2 and then weekly for 23 days, and at day 2 only for the Vori-Top group. Ocular inflammation was assessed weekly (Vori-Gel) using the modified Hackett-McDonald scoring system. Ocular tissue concentrations of voriconazole following SCo 1.7% voriconazole-thermogel (0.3 mL) injections were evaluated post euthanasia in 6 additional horses at 3 different time points. Three horses received bilateral injections at 2 h (n = 3, right eye (OD)) and 48 h (n = 3, left eye (OS)) prior to euthanasia, and 3 horses were injected unilaterally (OS), 7 days prior to euthanasia. Voriconazole-thermogel was easily injected and well tolerated in all cases, with no major adverse effects. On day 2, drug concentrations in tears were higher in the Vori-Top, but not statistically different from Vori-Gel groups. For the Vori-Gel group, voriconazole was non-quantifiable in the AH at any time point. Total voriconazole concentrations in the cornea were above 0.5 μg/g (the target minimum inhibitory concentration (MIC) for Aspergillus sp.) for up to 48 h; however, concentrations were below this MIC at 7 days post treatment. Conclusions: Voriconazole-thermogel was easily and safely administered to horses, and provided 48 h of sustained release of voriconazole into the cornea. This drug delivery system warrants further clinical evaluation.

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Sustained-release voriconazole-thermogel for subconjunctival injection in horses: ocular toxicity and in-vivo studies

et al. 2020

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“…All tests were performed in the order listed to minimize interference between tests; at least 10 minutes lapsed between some tests to permit the ocular surface to recover. 20,21 All tests were conducted in the right eye, followed by the left eye unless otherwise specified.…”

Section: Study Population and Designmentioning

confidence: 99%

“…Each dot represents the mean value of both eyes for a given individual, and the horizontal line indicates the median value of the group; *P , 0.05, ****P , 0.0001. lissamine green (Green Glo Lissamine Green Ophthalmic Strips; Amcon Laboratories, Inc) were used to assess ocular surface health and scored as described in Supplemental Digital Content 1 (see Appendix 1, http://links.lww.com/ICO/A873). 20 Intraocular pressure was measured by applanation tonometry (Tonopen XL; Medtronic Solan, Jacksonville, FL) after applying 0.5% proparacaine (Alcon Inc, Fort Worth, TX). Ultrasound pachymetry (Pachette 3; DGH Technology, Inc, Exton, PA) was performed as previously described.…”

Section: Tear Film Breakup Time and Ocular Surface Stainingmentioning

confidence: 99%

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

Leonard

Stewart

Shaw

et al. 2019

Cornea

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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, ADDEaffected 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, ADDEaffected WHWTs may prove a valuable naturally occurring ADDE model for investigating underlying pathophysiological mechanisms and the development of novel therapeutics.

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“…In general, topical treatment was well tolerated by patients. Findings using the SPOTS system included mild conjunctival hyperemia in all dogs following the last USP measurement of each day. Moderate conjunctival hyperemia was noted in three to four subjects on days 7, 9, and 10.…”

Section: Resultsmentioning

confidence: 99%

Effects of 5% sodium chloride ophthalmic ointment on thickness and morphology of the normal canine cornea

Samuel

Thomasy

Calderon

et al. 2018

Veterinary Ophthalmology

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The SPOTS System: An Ocular Scoring System Optimized for Use in Modern Preclinical Drug Development and Toxicology

Abstract: The SPOTS systems provide criteria that stand to enhance the applicability of semiquantitative scoring criteria to the full range of laboratory species, in the context of modern approaches to ocular therapeutics and drug delivery and drug and device development.

Cited by 78 publications

References 37 publications

Sustained-release voriconazole-thermogel for subconjunctival injection in horses: ocular toxicity and in-vivo studies

Sustained-release voriconazole-thermogel for subconjunctival injection in horses: ocular toxicity and in-vivo studies

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

Effects of 5% sodium chloride ophthalmic ointment on thickness and morphology of the normal canine cornea

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