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Article ; Online: Diagnosis of Dry Eye Disease Using Principal Component Analysis: A Study in Animal Models of the Disease.

Honkanen, Robert / Nemesure, Barbara / Huang, Liqun / Rigas, Basil

2021 Volume 46, Issue 5, Page(s) 622–629

Abstract: Purpose: To evaluate whether principal component analysis (PCA) can assess various diagnostic tests of dry eye disease (DED), providing a simplified, more informative measure of disease status than individual clinical test parameters (ICTP).: ... ...

Abstract	Purpose: To evaluate whether principal component analysis (PCA) can assess various diagnostic tests of dry eye disease (DED), providing a simplified, more informative measure of disease status than individual clinical test parameters (ICTP). Materials and methods: ICTP were analyzed using PCA in two groups of normal rabbits (Groups 1 and 2). Group 3, not truly normal, was also assessed. DED was induced in Group 1 by complete dacryoadenectomy; in Groups 2 and 3 by injection of concanavalin A. Tear break up time, tear osmolarity, Schirmer's tear test and rose bengal staining were the ICTP measured in all groups. Statistical analysis including descriptive statistics, t test, correlation coefficients and PCA was done. PCA using ICTP data from Group 1 generated axes; Group 2 and 3 were plotted over these axes. Results: All groups had induction of DED. Correlations for all ICTP were in the correct direction and were strongest for Group 1 and weakest in Group 3. PCA clearly separated DED and normal eyes. Principal component (PC) 1, made up of nearly equal contributions from the four clinical tests, explained 73% of the variation and provided a means to separate normal from DED. PC 1 values under 0.52 can be mathematically defined as DED. Of all pairwise comparisons, PC 1 vs PC 2 and PC 1 vs PC 3 were the most informative providing excellent spatial separation and additional information regarding DED status. Conclusions: PCA proved useful for evaluating DED providing a simpler, more comprehensive assessment than ICTP. PC 1 is a valuable, clinically relevant, and informative metric for DED status and severity having superior diagnostic value and statistical strength compared to ICTP. Spatial information on biplots of PC 1 vs PC 3 is also informative. PCA, and specifically PC 1, has the potential to serve as a biomarker for DED.
MeSH term(s)	Animals ; Diagnostic Techniques, Ophthalmological ; Disease Models, Animal ; Dry Eye Syndromes/diagnosis ; Dry Eye Syndromes/physiopathology ; Male ; Osmolar Concentration ; Principal Component Analysis/methods ; Rabbits ; Tears/chemistry ; Tears/physiology
Language	English
Publishing date	2021-01-14
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	82079-9
ISSN	1460-2202 ; 0271-3683
ISSN (online)	1460-2202
ISSN	0271-3683
DOI	10.1080/02713683.2020.1830115
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Article ; Online: A case of facultative ophthalmomyiasis externa due to Calliphoridae and review of the literature.

Wolek, Michael / Tourmouzis, Konstantinos / Garcia, Armando / Byrd, Jason / Weissbart, Sarah / Boyle, Nariman / Honkanen, Robert

American journal of ophthalmology case reports

2023 Volume 30, Page(s) 101822

Abstract: Purpose: To describe a case of bilateral facultative ophthalmomyiasis externa due to Calliphoridae in a 30-year-old male assault victim at a suburban hospital in New York and review the relevant literature.: Observations: An adult male was found to ... ...

Abstract	Purpose: To describe a case of bilateral facultative ophthalmomyiasis externa due to Calliphoridae in a 30-year-old male assault victim at a suburban hospital in New York and review the relevant literature. Observations: An adult male was found to have maggot infestation of both eyes and severe secondary injury to the left cornea and ocular surface. He was treated with manual larvae removal, oral ivermectin, broad spectrum IV antibiotics, and topical antibiotics. Anterior segment reconstruction was required. Conclusions and importance: We report the first case of ophthalmomyiasis due to Calliphoridae in the United States and document the vision threatening potential of this rare condition. Timely examination by an ophthalmologist with early debridement may help prevent vision-threatening sequelae.
Language	English
Publishing date	2023-02-19
Publishing country	United States
Document type	Case Reports
ISSN	2451-9936
ISSN (online)	2451-9936
DOI	10.1016/j.ajoc.2023.101822
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Article ; Online: The Antiangiogenic Effect and Ocular Pharmacology of Novel Modified Nonsteroidal Anti-Inflammatory Drugs in the Treatment of Oxygen-Induced Retinopathy.

Huang, Wei / Huang, Liqun / Wen, Ziyi / Honkanen, Robert A / Rigas, Basil

Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics

2023 Volume 39, Issue 4, Page(s) 279–289

Abstract: Purpose: ...

Abstract	Purpose:
MeSH term(s)	Humans ; Animals ; Mice ; Infant, Newborn ; Oxygen ; Retinal Vessels ; Animals, Newborn ; Tissue Distribution ; Retinal Diseases/drug therapy ; Angiogenesis Inhibitors/pharmacology ; Angiogenesis Inhibitors/therapeutic use ; Anti-Inflammatory Agents/therapeutic use ; Disease Models, Animal ; Mice, Inbred C57BL ; Retinal Neovascularization/chemically induced ; Retinal Neovascularization/drug therapy ; Retinopathy of Prematurity/drug therapy
Chemical Substances	Oxygen (S88TT14065) ; OXT-328 ; Angiogenesis Inhibitors ; Anti-Inflammatory Agents
Language	English
Publishing date	2023-05-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1237021-6
ISSN	1557-7732 ; 1080-7683
ISSN (online)	1557-7732
ISSN	1080-7683
DOI	10.1089/jop.2022.0113
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Article ; Online: A Rabbit Model of Aqueous-Deficient Dry Eye Disease Induced by Concanavalin A Injection into the Lacrimal Glands: Application to Drug Efficacy Studies.

Honkanen, Robert A / Huang, Liqun / Rigas, Basil

Journal of visualized experiments : JoVE

2020 , Issue 155

Abstract: Dry eye disease (DED), a multifactorial inflammatory disease of the ocular surface, affects 1 in 6 humans worldwide with staggering implications for quality of life and health care costs. The lack of informative animal models that recapitulate its key ... ...

Abstract	Dry eye disease (DED), a multifactorial inflammatory disease of the ocular surface, affects 1 in 6 humans worldwide with staggering implications for quality of life and health care costs. The lack of informative animal models that recapitulate its key features impedes the search for new therapeutic agents for DED. Available DED animal models have limited reproducibility and efficacy. A model is presented here in which DED is induced by injecting the mitogen concanavalin A (Con A) into the orbital lacrimal glands of rabbits. Innovative aspects of this model are the use of ultrasound (US) guidance to ensure optimal and reproducible injection of Con A into the inferior lacrimal gland; injection of Con A into all orbital lacrimal glands that limits compensatory production of tears; and use of periodic repeat injections of Con A that prolong the state of DED at will. DED and its response to test agents are monitored with a panel of parameters that assess tear production, the stability of the tear film, and the status of the corneal and conjunctival mucosa. They include tear osmolarity, tear break-up time, Schirmer's tear test, rose bengal staining, and tear lactoferrin levels. The induction of DED and the monitoring of its parameters are described in detail. This model is simple, robust, reproducible, and informative. This animal model is suitable for the study of tear physiology and of the pathophysiology of DED as well as for the assessment of the efficacy and safety of candidate agents for the treatment of DED.
MeSH term(s)	Animals ; Concanavalin A/adverse effects ; Disease Models, Animal ; Dry Eye Syndromes/chemically induced ; Female ; Humans ; Injections ; Lacrimal Apparatus/drug effects ; Male ; Quality of Life/psychology ; Rabbits ; Reproducibility of Results
Chemical Substances	Concanavalin A (11028-71-0)
Language	English
Publishing date	2020-01-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/59631
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Article ; Online: An Improved Ocular Impression Cytology Method: Quantitative Cell Transfer to Microscope Slides Using a Novel Polymer.

Master, Adam / Huang, Wei / Huang, Liqun / Honkanen, Robert / Rigas, Basil

Current eye research

2021 Volume 47, Issue 1, Page(s) 41–50

Abstract: Purpose: To develop a more efficient impression cytology (IC) method for the transfer of ocular surface cells onto glass microscope slides for cytochemical, immunocytochemical, and immunofluorescence studies.: Methods: Cells are lifted off the ocular ...

Abstract	Purpose: To develop a more efficient impression cytology (IC) method for the transfer of ocular surface cells onto glass microscope slides for cytochemical, immunocytochemical, and immunofluorescence studies. Methods: Cells are lifted off the ocular surface with a mixed cellulose ester membrane and then firmly attached to a glass slide using a novel triblock copolymer comprised of collagen type I, polyethylenimine and poly-L-lysine (CPP), and crosslinking cells and glass slide by heating and cooling. The membrane is removed intact after softening it with a butanol/ethanol solution. Transfer of cells is complete in about 10-15 minutes and is ready for staining. The efficiency of our cell transfer method was compared to current methods based on poly-L-lysine and albumin paste. Results: Our method ensured almost complete transfer of cells. In contrast, the transfer of rabbit conjunctiva cells onto poly-L-lysine-covered slides was 37.5 ± 6.3% lower, and onto albumin-paste covered slides 62.5 ± 5.6% lower (mean ± SD); the transfer of rabbit goblet cells was even less efficient. The new method was also more efficient for transfer of cells from human oral mucosa obtained by IC. Transferred cells were successfully stained with H&E, chemiluminescence, and immunofluorescence agents. Using our method, we stained ocular surface cells for S100A4 and ATF4, both of which play a role in the pathophysiology of dry eye disease. We obtained similar results with oral mucosal cells, suggesting the generalizability of our approach. We propose an explanation for the strong adhesion of cells to the glass slide, which is based on their interactions with the triblock copolymer. Conclusions: We developed a novel approach for the efficient and rapid transfer of cells obtained by IC onto glass microscope slides using a novel copolymer. Compared to available methods, our improved approach makes IC robust and simple, and should increase its diagnostic yield and clinical applicability.
MeSH term(s)	Aged ; Animals ; Cytological Techniques/trends ; Female ; Goblet Cells/cytology ; Humans ; Male ; Microscopy/methods ; Middle Aged ; Models, Animal ; Polymers/pharmacology ; Rabbits
Chemical Substances	Polymers
Language	English
Publishing date	2021-11-27
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	82079-9
ISSN	1460-2202 ; 0271-3683
ISSN (online)	1460-2202
ISSN	0271-3683
DOI	10.1080/02713683.2021.1951300
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Jg. 1995 - 2021: Lesesall (1.OG)
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Article: A rabbit model of aqueous-deficient dry eye disease induced by concanavalin a injection into the lacrimal glands: application to drug efficacy studies

Honkanen, Robert A / Huang, Liqun / Rigas, Basil

Journal of visualized experiments. 2020 Jan. 24, , no. 155

2020

Abstract	Dry eye disease (DED), a multifactorial inflammatory disease of the ocular surface, affects 1 in 6 humans worldwide with staggering implications for quality of life and health care costs. The lack of informative animal models that recapitulate its key features impedes the search for new therapeutic agents for DED. Available DED animal models have limited reproducibility and efficacy. A model is presented here in which DED is induced by injecting the mitogen concanavalin A (Con A) into the orbital lacrimal glands of rabbits. Innovative aspects of this model are the use of ultrasound (US) guidance to ensure optimal and reproducible injection of Con A into the inferior lacrimal gland; injection of Con A into all orbital lacrimal glands that limits compensatory production of tears; and use of periodic repeat injections of Con A that prolong the state of DED at will. DED and its response to test agents are monitored with a panel of parameters that assess tear production, the stability of the tear film, and the status of the corneal and conjunctival mucosa. They include tear osmolarity, tear break-up time, Schirmer's tear test, rose bengal staining, and tear lactoferrin levels. The induction of DED and the monitoring of its parameters are described in detail. This model is simple, robust, reproducible, and informative. This animal model is suitable for the study of tear physiology and of the pathophysiology of DED as well as for the assessment of the efficacy and safety of candidate agents for the treatment of DED.
Keywords	animal models ; animal physiology ; concanavalin A ; cornea ; drugs ; eye diseases ; health care costs ; humans ; lacrimal apparatus ; lactoferrin ; mitogens ; monitoring ; mucosa ; osmolarity ; pathophysiology ; quality of life ; rabbits ; staining ; tears ; therapeutics ; ultrasonics
Language	English
Dates of publication	2020-0124
Size	p. e59631.
Publishing place	Journal of Visualized Experiments
Document type	Article
ZDB-ID	2259946-0
ISSN	1940-087X
ISSN	1940-087X
DOI	10.3791/59631
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Relationship between sleep position and glaucoma progression.

Kaplowitz, Kevin / Dredge, Justin / Honkanen, Robert

Current opinion in ophthalmology

2019 Volume 30, Issue 6, Page(s) 484–490

Abstract: Purpose of review: As humans spend a considerable portion of life in the horizontal position, it is vital to better understand the effect of sleep position on glaucoma.: Recent findings: The mean positional increase from the supine position to the ... ...

Abstract	Purpose of review: As humans spend a considerable portion of life in the horizontal position, it is vital to better understand the effect of sleep position on glaucoma. Recent findings: The mean positional increase from the supine position to the lateral decubitus position (LDP) in recent literature is less than 2 mmHg for each eye in its dependent position and less than 1 mmHg in the nondependent position. The right LDP is most commonly favored sleeping position. Some evidence suggests that the positional increases persist and so could lead to worse glaucomatous progression in the dependent eye. However, multiple studies failed to find a strong association. Ideally future research will identify risk factors for higher positional increases to identify patients who may benefit from a change in sleep position. To date, medications and argon laser trabeculoplasty have been ineffective in blunting the positional increase, although glaucoma surgery does reduce it. Raising the head of the bed has been linked with blunting the increase as well. Summary: Certain sleeping positions appear to be associated with higher intraocular pressure, although the association between sleep position and glaucoma progression is not as clear.
MeSH term(s)	Disease Progression ; Glaucoma/diagnosis ; Glaucoma/physiopathology ; Humans ; Intraocular Pressure/physiology ; Posture/physiology ; Sleep/physiology ; Tonometry, Ocular
Language	English
Publishing date	2019-10-07
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1049383-9
ISSN	1531-7021 ; 1040-8738
ISSN (online)	1531-7021
ISSN	1040-8738
DOI	10.1097/ICU.0000000000000612
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Article ; Online: NSAID-induced corneal melt: Clinical importance, pathogenesis, and risk mitigation.

Rigas, Basil / Huang, Wei / Honkanen, Robert

Survey of ophthalmology

2019 Volume 65, Issue 1, Page(s) 1–11

Abstract: Corneal melt, an ophthalmological condition in which corneal epithelium is lost accompanied by thinning of the corneal stroma, can lead to corneal perforation and cause loss of vision. Corneal melt is the most serious side effect of topical nonsteroidal ... ...

Abstract	Corneal melt, an ophthalmological condition in which corneal epithelium is lost accompanied by thinning of the corneal stroma, can lead to corneal perforation and cause loss of vision. Corneal melt is the most serious side effect of topical nonsteroidal anti-inflammatory drugs (NSAIDs), one of the topical treatments of ocular inflammation. NSAID-induced corneal melt (NICM), initially doubted, is real, having been reported by multiple groups. NICM is induced by all but one of the approved ocular NSAIDs and occurs usually in patients whose cornea is compromised by ocular surgery, diabetes, or autoimmune diseases. Its true incidence, most likely low, remains unknown. NSAID dose and duration of treatment may be important for NICM. NICM appears to evolve in two stages: the epithelial stage-marked by a corneal epithelial defect, reduced eicosanoid levels, leukocyte infiltration, and matrix metalloproteinase-facilitated desquamation-and the stromal stage, characterized by degradation of stromal collagen by activated matrix metalloproteinases. Awareness of this ominous side effect, its risk factors, and the need for prompt action once diagnosed, including NSAID discontinuation, will help mitigate the risk of NICM. Further understanding of NICM and development of efficacious treatments or safer alternatives should help eliminate this rare, but severe, side effect of ocular NSAIDs.
MeSH term(s)	Administration, Topical ; Anti-Inflammatory Agents, Non-Steroidal/administration & dosage ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Cornea/diagnostic imaging ; Cornea/drug effects ; Corneal Diseases/chemically induced ; Corneal Diseases/diagnosis ; Humans ; Ophthalmic Solutions ; Risk Factors ; Slit Lamp Microscopy
Chemical Substances	Anti-Inflammatory Agents, Non-Steroidal ; Ophthalmic Solutions
Language	English
Publishing date	2019-07-12
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	391346-6
ISSN	1879-3304 ; 0039-6257
ISSN (online)	1879-3304
ISSN	0039-6257
DOI	10.1016/j.survophthal.2019.07.001
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Article ; Online: Establishment of a Severe Dry Eye Model Using Complete Dacryoadenectomy in Rabbits.

Honkanen, Robert A / Huang, Liqun / Huang, Wei / Rigas, Basil

Journal of visualized experiments : JoVE

2020 , Issue 155

Abstract: Dry eye disease (DED) is a complex disease with multiple etiologies and variable symptoms, having ocular surface inflammation as its key pathophysiologic step. Despite advances in our understanding of DED, significant knowledge gaps remain. Advances are ... ...

Abstract	Dry eye disease (DED) is a complex disease with multiple etiologies and variable symptoms, having ocular surface inflammation as its key pathophysiologic step. Despite advances in our understanding of DED, significant knowledge gaps remain. Advances are limited in part due to the lack of informative animal models. The authors recently reported on a method of DED induced by injecting all orbital lacrimal gland (LG) tissues with the lectin concanavalin A. Here, we report a novel model of aqueous-deficient DED based on the surgical resection of all orbital LG (dacryoadenectomy) tissues. Both methods use rabbits because of their similarity to human eyes in terms of the size and structure of the ocular surface. One week after removal of the nictitating membrane, the orbital superior LG was surgically removed under anesthesia, followed by removal of the palpebral superior LG, and finally removal of the inferior LG. Dacryoadenectomy induced severe DED, evidenced by a marked reduction in the tear break up time test and the Schirmer's tear test, and significantly increased tear osmolarity and rose bengal staining. Dacryoadenectomy-induced DED lasted at least eight weeks. There were no complications and animals tolerated the procedure well. The technique can be mastered relatively easily by those with adequate surgical experience and appreciation of the relevant rabbit anatomy. Since this model recapitulates the features of human aqueous-deficient DED, it is suitable for studies of ocular surface homeostasis, DED, and candidate therapeutics.
MeSH term(s)	Animals ; Disease Models, Animal ; Dry Eye Syndromes/diagnosis ; Female ; Humans ; Lacrimal Apparatus/physiopathology ; Lacrimal Apparatus/surgery ; Lacrimal Apparatus Diseases/surgery ; Male ; Rabbits ; Tears/metabolism
Language	English
Publishing date	2020-01-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/60126
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Article: Non-contact terahertz spectroscopic measurement of the intraocular pressure through corneal hydration mapping.

Chen, Andrew / Virk, Arjun / Harris, Zachery / Abazari, Azin / Honkanen, Robert / Arbab, M Hassan

Biomedical optics express

2021 Volume 12, Issue 6, Page(s) 3438–3449

Abstract: Elevated intraocular pressure (IOP) results in endothelial layer damage that can induce corneal hydration perturbations. We investigated the potential of terahertz spectroscopy in measuring the IOP levels through mapping corneal water content. We ... ...

Abstract	Elevated intraocular pressure (IOP) results in endothelial layer damage that can induce corneal hydration perturbations. We investigated the potential of terahertz spectroscopy in measuring the IOP levels through mapping corneal water content. We controlled the IOP levels in
Language	English
Publishing date	2021-05-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2572216-5
ISSN	2156-7085
ISSN	2156-7085
DOI	10.1364/BOE.423741
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