Publications by authors named "Atsuki Fukushima"

163 Publications

Clinical profile and visual outcome of intraocular inflammation associated with cat-scratch disease in Japanese patients.

Jpn J Ophthalmol 2021 Apr 2. Epub 2021 Apr 2.

Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku City, Kochi, 783-8505, Japan.

Purpose: To evaluate intraocular inflammation in Japanese patients with cat-scratch disease (CSD).

Study Design: Retrospective clinical chart review.

Patients And Methods: The cases of 15 consecutive patients (19 affected eyes) in Kochi Prefecture, Japan who were serologically positive for Bartonella henselae or Bartonella quintana infection in association with intraocular inflammation were reviewed. The clinical manifestations, ocular complications, and treatment modalities were recorded. The clinical charts and photographic records were also reviewed for evidence of optic disc lesions, macular star, foci of chorioretinitis, and other findings.

Results: Thirteen patients reported fever before or at the time of the initial presentation. Ten of 11 patients with decreased visual acuity manifested neuroretinitis, and the remaining patient showed retinochoroiditis with macular involvement. One patient with a visual field defect manifested branch retinal artery occlusion. Three patients without visual disturbance presented with fever of unknown cause. Discrete white retinal or retinochoroidal lesions were the most common findings (84% of eyes, 87% of patients), followed by retinal hemorrhage (63% of eyes, 80% of patients), optic disc lesions (63% of eyes, 73% of patients), serous retinal detachment (53% of eyes, 67% of patients), and macular star (47% of eyes, 60% of patients).

Conclusion: White retinal or retinochoroidal foci were the most common ocular posterior segment manifestations of CSD in this patient population. A diagnosis of CSD should be suspected in patients with fever and chorioretinal white spots, and the absence of neuroretinitis or macular star does not exclude the possibility of intraocular inflammation in CSD.
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http://dx.doi.org/10.1007/s10384-021-00835-7DOI Listing
April 2021

Optic Neuropathy with Headache and Palpable Temporal Arteries Due to Hypertrophic Pachymeningitis Rather than Giant Cell Arteritis.

Ocul Immunol Inflamm 2021 Apr 1:1-4. Epub 2021 Apr 1.

Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University, Nankoku City, Kochi, Japan.

: To report a case of optic neuropathy diagnosed by color Doppler ultrasonography and Gadolinium-enhanced cerebral magnetic resonance imaging (MRI).: A 79-year-old woman presented with headache and vision loss in her left eye. Although her bilateral temporal arteries were palpable and rope-like, color Doppler ultrasonography showed normal flow in both arteries with no signs of arteritis. MRI revealed increased enhancement of the pachymeninges enveloping both cerebral hemispheres, suggestive of hypertrophic pachymeningitis.: Symptoms and laboratory data are similar for both hypertrophic pachymeningitis and giant cell arteritis (GCA). The present case suggests the utility of ultrasonography and MRI as rapid, convenient, and noninvasive tools for differential diagnosis of optic neuropathy.
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http://dx.doi.org/10.1080/09273948.2021.1881561DOI Listing
April 2021

[QUANTIFICATION OF CONJUNCTIVAL HYPEREMIA IN RABBITS USING ANALYSIS SOFTWARE].

Arerugi 2021 ;70(1):26-32

Department of Ophthalmology, Kochi Medical School.

Background/purpose: In a method evaluating conjunctival hyperemia using rabbits, it is common to visually grade the degree of vasodilation. However, this method is limited in evaluating consecutive value and in reproducibility. We quantified the degree of conjunctival hyperemia in rabbits as the area ratio of blood vessels by image analysis, and compared the vascular area percentage calculated by image analysis with the hyperemia score.

Methods: The conjunctiva was photographed before and after the instillation of 0.1% arachidonic acid using a digital medical scope VersaCam (Nidek Co., Ltd.). Next, the area of the conjunctival blood vessels occupying the area of interest was calculated using hyperemia analysis software. The hyperemia score was visually graded for the degree of conjunctiva vasodilation. Furthermore, the hyperemia score and the vascular area ratio were compared.

Results: Fifteen minutes after the instillation of arachidonic acid, the area ratio of the blood vessels in the conjunctiva increased significantly and gradually decreased over time. This trend correlated with the hyperemia score.

Conclusion: We found that the degree of conjunctival hyperemia in rabbits can be evaluated numerically and quantitatively. This method is considered to be useful for evaluating conjunctival hyperemia in allergic conjunctival diseases.
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http://dx.doi.org/10.15036/arerugi.70.26DOI Listing
February 2021

In Vitro and In Vivo Evaluation of Three Newly Isolated Bacteriophage Candidates, phiEF7H, phiEF14H1, phiEF19G, for Treatment of Endophthalmitis.

Microorganisms 2021 Jan 20;9(2). Epub 2021 Jan 20.

Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University, Kochi 783-8505, Japan.

Post-operative endophthalmitis caused by spp. progresses rapidly and often results in substantial and irreversible vision loss. Therefore, novel alternative treatments that are effective against enterococcal endophthalmitis are required. Bacteriophage therapy has the potential to be an optional therapy for infectious diseases. Therefore, we investigated the therapeutic potential of three newly isolated enterococcal phages, phiEF7H, phiEF14H1, and phiEF19G, in -induced endophthalmitis. These phages could lyse the broad-range , including strains derived from endophthalmitis and vancomycin-resistant in vitro, as determined by the streak test. Morphological and genomic analyses revealed that these phages were classified into the genus . The whole genomes of these phages contained 143,399, 143,280, and 143,400 bp, respectively. Endophthalmitis was induced in mice by injection of three strains of derived from post-operative endophthalmitis or vancomycin-resistant strains into the vitreous body. The number of viable bacteria and infiltration of neutrophils in the eye were both decreased by intravitreous injection of phiEF7H, phiEF14H1, and phiEF19G 6 h after injection of all strains. Thus, these results suggest that these newly isolated phages may serve as promising candidates for phage therapy against endophthalmitis.
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http://dx.doi.org/10.3390/microorganisms9020212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909552PMC
January 2021

Japanese guidelines for allergic conjunctival diseases 2020.

Allergol Int 2020 Jul 25;69(3):346-355. Epub 2020 Apr 25.

Department of Ophthalmology, Tsurumi University School of Dental Medicine, Kanagawa, Japan.

The definition, classification, pathogenesis, test methods, clinical findings, criteria for diagnosis, and therapies of allergic conjunctival disease are summarized based on the Guidelines for Clinical Management of Allergic Conjunctival Disease 2019. Allergic conjunctival disease is defined as "a conjunctival inflammatory disease associated with a Type I allergy accompanied by some subjective or objective symptoms." Allergic conjunctival disease is classified into allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, and giant papillary conjunctivitis. Representative subjective symptoms include ocular itching, hyperemia, and lacrimation, whereas objective symptoms include conjunctival hyperemia, swelling, folliculosis, and papillae. Patients with vernal keratoconjunctivitis, which is characterized by conjunctival proliferative changes called giant papilla accompanied by varying extents of corneal lesion, such as corneal erosion and shield ulcer, complain of foreign body sensation, ocular pain, and photophobia. In the diagnosis of allergic conjunctival diseases, it is required that type I allergic diathesis is present, along with subjective and objective symptoms accompanying allergic inflammation. The diagnosis is ensured by proving a type I allergic reaction in the conjunctiva. Given that the first-line drug for the treatment of allergic conjunctival disease is an antiallergic eye drop, a steroid eye drop will be selected in accordance with the severity. In the treatment of vernal keratoconjunctivitis, an immunosuppressive eye drop will be concomitantly used with the abovementioned drugs.
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http://dx.doi.org/10.1016/j.alit.2020.03.005DOI Listing
July 2020

Reduced steroid-induced intraocular pressure elevation in tacrolimus-treated refractory allergic ocular diseases.

Jpn J Ophthalmol 2020 Nov 7;64(6):568-576. Epub 2020 Oct 7.

Department of Ophthalmology, Tsurumi University Dental Hospital, Yokohama, Kanagawa, Japan.

Purpose: To determine whether topical tacrolimus can lessen steroid-induced intraocular pressure (IOP) elevation.

Study Design: Open cohort post hoc analysis study.

Methods: Five hundred eleven patients with vernal keratoconjunctivitis or atopic keratoconjunctivitis (mean age 17.0 ± 9.2 years) were studied. All 511 patients were treated with topical tacrolimus with or without topical steroids, and the changes in IOP were measured monthly for 3 months. The elevation in IOP induced by use of topical steroids was calculated using mixed linear regression analyses. The relationship between the elevation in IOP within 4 weeks and the use or nonuse of tacrolimus reported in published data was analyzed using metaregression analysis to estimate the effects of tacrolimus on the IOP in eyes treated with topical steroids.

Results: The mean topical steroid-induced IOP elevation in tacrolimus-treated eyes was lower, by 5.2 mmHg (P = 0.04), than that in earlier published data without tacrolimus as the control. In the tacrolimus-treated eyes, the mean betamethasone-induced IOP elevation was 1.3 mmHg without discontinuation of the steroid. Metaregression analysis indicated that glaucoma history and younger age had significant effects on topical steroid-induced IOP elevation, by 4.0 mmHg (P = 0.002) and 3.9 mmHg (P = 0.01), respectively. In tacrolimus-treated eyes, the most significant effect on the IOP was associated with glaucoma history or medication; however, its effect on the IOP was limited to 1.7 mmHg elevation (P = 0.006).

Conclusions: Topical tacrolimus may lessen the steroid-induced elevation in IOP in younger individuals and may be a good adjunctive therapy to avoid IOP elevation in refractory cases.
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http://dx.doi.org/10.1007/s10384-020-00774-9DOI Listing
November 2020

Current research progress in allergic conjunctival diseases.

Authors:
Atsuki Fukushima

Allergol Int 2020 Oct;69(4):485-486

Department of Ophthalmology, Kochi Medical School, Kochi, Japan. Electronic address:

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http://dx.doi.org/10.1016/j.alit.2020.08.003DOI Listing
October 2020

"Progress in Corneal Research and Practice in Japan and Abroad" - The 25th Annual Meeting of the Kyoto Cornea Club, November 29-30, 2019.

Cornea 2020 11;39 Suppl 1:S1-S2

Department of Ophthalmology, International University of Health and Welfare Medical School, Tokyo, Japan.

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http://dx.doi.org/10.1097/ICO.0000000000002483DOI Listing
November 2020

Time course of conjunctival hyperemia induced by omidenepag isopropyl ophthalmic solution 0.002%: a pilot, comparative study versus ripasudil 0.4.

BMJ Open Ophthalmol 2020 2;5(1):e000538. Epub 2020 Aug 2.

Department of Ophthalmology, Hiroshima University, Hiroshima, Japan.

Objective: We investigated the detailed time course of conjunctival hyperemia induced by omidenepag isopropyl ophthalmic solution 0.002% (omidenepag), a selective prostaglandin E2 receptor 2 agonist.

Methods And Analysis: We recruited 34 healthy subjects and administered omidenepag in the right eye and ripasudil 0.4% in the left eye. We evaluated conjunctival hyperemia using slit-lamp photography at baseline and after 15, 30, 60, 120, 180 and 360 min. The conjunctival hyperemia score was graded by three independent observers using a scale from 0 (none) to 3 (severe). We also evaluated conjunctival hyperemia by the pixel coverage of conjunctival blood vessels (per cent coverage) determined using a conjunctival hyperemia-analysing software.

Results: In omidenepag, the conjunctival hyperemia score and per cent coverage peaked at both 30 min (mean score±SD: 1.57±0.67 and 11.90%±3.66%, respectively) and then gradually decreased at 60 min (10.79%±3.32%) and 120 min (1.10±0.52) when they reached a level that was not significantly different from the baseline values. For ripasudil 0.4%, the peak time of the conjunctival hyperemia score and per cent coverage were both at 15 min (score: 2.42±0.54 and 15.26%±3.38%). The degree of conjunctival hyperemia was significantly higher for ripasudil 0.4% than that for omidenepag from 15 to 30 min in both the conjunctival hyperemia score and per cent coverage (p<0.007 by Bonferroni correction).

Conclusion: Conjunctival hyperemia induced by omidenepag gradually peaks to moderate severity, though weaker compared with that induced by ripasudil 0.4%, and subsides relatively quickly.
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http://dx.doi.org/10.1136/bmjophth-2020-000538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398095PMC
August 2020

Epidemiological aspects of allergic conjunctivitis.

Allergol Int 2020 Oct 9;69(4):487-495. Epub 2020 Jul 9.

Division of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Tottori, Japan.

The prevalence of ocular allergies has been increasing worldwide for the past several decades. The geographical distribution and hot spots of rhinoconjunctivitis have been documented in a global survey by the International Study of Asthma and Allergies in Childhood (ISAAC). ISAAC indicated that Africa, Latin America, and Japan were notable for their high prevalence of rhinoconjunctivitis. The outcomes of follow-up studies of regional differences and the characteristics of allergic conjunctivitis are summarized in this review. Currently, comorbid diseases and socioeconomic and environmental factors, including climate and air pollution, are proposed to contribute to the regional differences in the prevalence of allergic conjunctivitis. Of them, rhinitis has been shown repeatedly to be significantly associated with allergic conjunctivitis. Their mechanistic aspects on association with the prevalence of systemic allergic diseases have been reviewed by examining the birth cohort or in vitro analyses. A vision threatening form of ocular allergy, vernal keratoconjunctivitis, is prevalent in the African countries and Japan. Of the proposed associated factors, air pollution was shown to contribute not only to aggravating the symptoms but also to the increase in the incidence of its severe forms. Its mechanistic aspects are discussed in this review in the context of comorbid diseases.
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http://dx.doi.org/10.1016/j.alit.2020.06.004DOI Listing
October 2020

Strategic Outlook toward 2030: Japan's research for allergy and immunology - Secondary publication.

Allergol Int 2020 Oct 27;69(4):561-570. Epub 2020 Jun 27.

Division of Molecular Genetics, The Jikei University School of Medicine, Research Center for Medical Science, Tokyo, Japan. Electronic address:

Strategic Outlook toward 2030: Japan's Research for Allergy and Immunology (Strategy 2030) is the national research strategy based on Japan's Basic Law on Measures Against Allergic Diseases, a first of its kind worldwide. This strategy was established by a multi-disciplinary committee consisting of administrators of the Ministry of Health, Labour and Welfare of Japan, young and senior experts from various research societies and associations, and representatives of patient and public groups. Whereas the issues of transition, integration, and international collaboration have yet to be solved in this research realm in Japan, identification of unmet needs, digitization of information and transparent procedures, and strategic planning for complex problems (a process dubbed MIERUKA by the Toyota Way) are crucial to share and tackle the same vision and goals. The committee developed three specific actions focusing on preemptive treatment, interdisciplinarity and internationality, and life stage. The real success of Strategy 2030 is made by the spontaneous contributions of doctors, dentists, veterinarians, and other medical professionals; basic and clinical research scientists, research supporters, and pharmaceutical/medical device companies; manufacturers of food, healthcare, and home appliances; and patients, their families, and the public. The hope is to establish a stable society in which people can live long, healthy lives, as free as possible from allergic and immunological diseases, at each individual life stage. This article is based on a Japanese review first reported in Arerugi, introduces the developmental process and details of Strategy 2030.
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http://dx.doi.org/10.1016/j.alit.2020.04.006DOI Listing
October 2020

Air pollution significantly associated with severe ocular allergic inflammatory diseases.

Sci Rep 2019 12 3;9(1):18205. Epub 2019 Dec 3.

Division of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Yonago, Japan.

Ambient air pollution is a well-recognized risk for various diseases including asthma and heart diseases. However, it remains unclear whether air pollution may also be a risk of ocular allergic diseases. Using a web-based, nation-wide, cross-sectional study design, we examined whether the level of ambient air pollution is significantly associated with the prevalence of ocular allergic diseases. A web-based questionnaire was posted to invite the participants who are members of the Japan Ophthalmologist Association and their family members. The answers from 3004 respondents were used to determine whether there were significant associations between the level of the pollutants and the prevalence of ocular allergic diseases. The study period was between March to May 2017. The data of the air pollutants during 2012 to 2016 were obtained from the National Institute for Environmental Studies. The prevalence of allergic diseases was calculated by post stratification and examined for significant associations with the level of pollutants using multiple logistic regression analyses. The prevalence of seasonal allergic conjunctivitis, perennial allergic conjunctivitis, atopic keratoconjunctivitis (AKC), and vernal keratoconjunctivitis (VKC) in Japan was 45.4%, 14.0%, 5.3%, and 1.2%, respectively. The high prevalence of the severe forms of allergic conjunctivitis, including AKC and VKC, were significantly associated with the levels of the air pollutants. The prevalence of AKC was significantly associated with the levels of NO with an odds ratio (OR) of 1.23 (per quintile). The prevalence of VKC was significantly associated with the levels of NO and PM with ORs of 1.72 and 1.54 respectively. The significant associations between the prevalence of AKC and VKC and the levels of air pollutants indicate that clinicians need to be aware that air pollutants may pose serious risks of vision threatening severe ocular allergy.
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http://dx.doi.org/10.1038/s41598-019-54841-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890742PMC
December 2019

Amelioration of conjunctival giant papillae by dupilumab in patients with atopic keratoconjunctivitis.

J Allergy Clin Immunol Pract 2020 Mar 31;8(3):1152-1155. Epub 2019 Oct 31.

Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University, Kochi, Japan.

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http://dx.doi.org/10.1016/j.jaip.2019.10.011DOI Listing
March 2020

Miscellaneous Ocular Symptoms in a Case of Relapsing Polychondritis.

Ocul Immunol Inflamm 2019 Oct 30:1-3. Epub 2019 Oct 30.

Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University, Nankoku City, Kochi, Japan.

Purpose: To report a case of miscellaneous ocular symptoms associated with relapsing polychondritis (RP).

Case Report: A 58-year-old man presented with multiple ocular symptoms including both anterior and posterior scleritis, conjunctivitis, eyelid edema, eye movement disorder, keratitis, and retinopathy. Miscellaneous systemic inflammation in the right auricle as well as nasal and laryngeal cartilage was also evident together with vestibular and auditory nerve disorders. According to his clinical signs and the results of color Doppler ultrasonography, positron emission tomography and computed tomography, and a biopsy of the right auricle, we made a diagnosis of RP.

Conclusion: Given that RP is potentially fatal, it is important that the condition be diagnosed early and treated promptly. Ophthalmologists should be aware that RP is a potential cause of recurrent and refractory multiple ocular inflammatory disorders associated with systemic symptoms.
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http://dx.doi.org/10.1080/09273948.2019.1674892DOI Listing
October 2019

"Progress in Corneal Research and Practice in Japan and Abroad"-The 24th Annual Meeting of the Kyoto Cornea Club, November 30-December 1, 2018.

Cornea 2019 11;38 Suppl 1:S1-S2

Department of Biomedical Engineering, Faculty of Life and Medical Sciences, Doshisha University, Kyoto, Japan.

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http://dx.doi.org/10.1097/ICO.0000000000002123DOI Listing
November 2019

Recurrent Optic Perineuritis as the First Manifestation of Relapsing Polychondritis.

J Neuroophthalmol 2019 12;39(4):513-514

Departments of Ophthalmology and Visual Science (YM, KF, AF), Endocrinology, Metabolism, and Nephrology (YT), and Otolaryngology (MK), Kochi Medical School, Kochi University, Nankoku City, Japan.

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http://dx.doi.org/10.1097/WNO.0000000000000820DOI Listing
December 2019

Therapeutic Effects of Intravitreously Administered Bacteriophage in a Mouse Model of Endophthalmitis Caused by Vancomycin-Sensitive or -Resistant Enterococcus faecalis.

Antimicrob Agents Chemother 2019 11 22;63(11). Epub 2019 Oct 22.

Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University, Kochi, Japan.

Endophthalmitis due to infection with spp. progresses rapidly and often results in substantial and irreversible vision loss. Given that the frequency of this condition caused by vancomycin-resistant has been increasing, the development of novel therapeutics is urgently required. We have demonstrated the therapeutic potential of bacteriophage ΦEF24C-P2 in a mouse model of endophthalmitis caused by vancomycin-sensitive (EF24) or vancomycin-resistant (VRE2) strains of Phage ΦEF24C-P2 induced rapid and pronounced bacterial lysis in turbidity reduction assays with EF24, VRE2, and clinical isolates derived from patients with -related postoperative endophthalmitis. Endophthalmitis was induced in mice by injection of EF24 or VRE2 (1 × 10 cells) into the vitreous. The number of viable bacteria in the eye increased to >1 × 10 CFU, and neutrophil infiltration into the eye was detected as an increase in myeloperoxidase activity at 24 h after infection. A clinical score based on loss of visibility of the fundus as well as the number of viable bacteria and the level of myeloperoxidase activity in the eye were all significantly decreased by intravitreous injection of ΦEF24C-P2 6 h after injection of EF24 or VRE2. Whereas histopathologic analysis revealed massive infiltration of inflammatory cells and retinal detachment in vehicle-treated eyes, the number of these cells was greatly reduced and retinal structural integrity was preserved in phage-treated eyes. Our results thus suggest that intravitreous phage therapy is a potential treatment for endophthalmitis caused by vancomycin-sensitive or -resistant strains of .
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http://dx.doi.org/10.1128/AAC.01088-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811408PMC
November 2019

Severity Classification of Conjunctival Hyperaemia by Deep Neural Network Ensembles.

J Ophthalmol 2019 2;2019:7820971. Epub 2019 Jun 2.

Department of Ophthalmology and Visual Science, Kochi Medical School, Nankoku, Japan.

Conjunctival hyperaemia is a common clinical ophthalmological finding and can be a symptom of various ocular disorders. Although several severity classification criteria have been proposed, none include objective severity criteria. Neural networks and deep learning have been utilised in ophthalmology, but not for the purpose of classifying the severity of conjunctival hyperaemia objectively. To develop a conjunctival hyperaemia grading software, we used 3700 images as the training data and 923 images as the validation test data. We trained the nine neural network models and validated the performance of these networks. We finally chose the best combination of these networks. The DenseNet201 model was the best individual model. The combination of the DenseNet201, DenseNet121, VGG19, and ResNet50 were the best model. The correlation between the multimodel responses, and the vessel-area occupied was 0.737 ( < 0.01). This system could be as accurate and comprehensive as specialists but would be significantly faster and consistent with objective values.
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http://dx.doi.org/10.1155/2019/7820971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589312PMC
June 2019

Topical Tacrolimus for Chronic Allergic Conjunctival Disease with and without Atopic Dermatitis.

Curr Eye Res 2019 07 5;44(7):796-805. Epub 2019 Apr 5.

k Okamoto Eye Clinic , Ehime , Japan.

: This study evaluated the efficacy of topical 0.1% tacrolimus ophthalmic suspension for treating chronic allergic conjunctival disease with and without atopic dermatitis. : This study was conducted as a prospective observational post-market survey. Our large-scale study protocol was accepted by the Pharmaceuticals and Medical Devices Agency in Japan and included patients who were prescribed topical tacrolimus for the treatment of chronic allergic conjunctival disease from May 2008 to Aug 2010 in Japan. Topical tacrolimus was instilled 2 times daily for 6 months. The primary endpoint was the change from baseline in papillae-limbus-cornea clinical signs score (based on the presence of papillae, giant papillae, Trantas' dots, limbal swelling, and corneal epithelial signs). Remission rate following topical tacrolimus treatment was investigated using generalized estimating equations. : A total of 1821 subjects were included in the analyses. Six months into treatment, 83.0% and 87.7% of subjects with and without atopic dermatitis, respectively, were in remission (based on the papillae-limbus-cornea grading score). Topical tacrolimus treatment was equally effective in improving papillae-limbus-cornea grading scores from baseline in both study groups after 6 months of treatment. Additionally, the odds ratio for remission increased over time. The concomitant use of topical steroids improved papillae-limbus-cornea grading scores, including papillary signs with a statistically significant, but low odds ratio. : Tacrolimus ophthalmic suspension is useful for treating chronic allergic conjunctival disease with and without atopic dermatitis. Clinical response to local tacrolimus therapy is dependent upon treatment duration.
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http://dx.doi.org/10.1080/02713683.2019.1600197DOI Listing
July 2019

Unilateral serous retinal detachment with choroidal thickening as a first presenting sign of acute myeloid leukemia.

Am J Ophthalmol Case Rep 2019 Jun 23;14:51-54. Epub 2019 Feb 23.

Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University, Nankoku City, Kochi, Japan.

Purpose: Serous retinal detachment is rare in leukemia, but bilateral or unilateral cases have been reported as the presenting sign of acute leukemia or the first sign of relapsing leukemia. We here report a case of unilateral serous retinal detachment with choroidal thickening before the detection of atypical lymphocytes or myeloblasts as the initial manifestation of subsequently diagnosed acute myeloid leukemia.

Observations: A 43-year-old woman presented with serous retinal detachment in her left eye. Choroidal thickening was also revealed by B-scan ultrasonography and optical coherence tomography. Atypical lymphocytes or myeloblasts were not apparent on hematologic analysis at initial presentation, but an increased leukocyte count and the presence of 40% blasts in a peripheral smear were detected 1 month later. A bone marrow biopsy led to a diagnosis of acute promyelocytic leukemia. The retinal detachment and choroidal thickening showed amelioration 4 days after the onset of chemotherapy and had resolved 2 months later.

Conclusions And Importance: The present findings suggest that, although retinal detachment is not a common manifestation in patients with leukemia, unilateral serous retinal detachment with choroidal thickening may be a presenting sign of acute myeloid leukemia.
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http://dx.doi.org/10.1016/j.ajoc.2019.02.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396195PMC
June 2019

Evaluation of offset of conjunctival hyperemia induced by a Rho-kinase inhibitor; 0.4% Ripasudil ophthalmic solution clinical trial.

Sci Rep 2019 03 6;9(1):3755. Epub 2019 Mar 6.

Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University, Nankoku City, Kochi, Japan.

Glaucoma leads to irreversible blindness. Numerous anti-glaucoma eye drops have been developed. Unfortunately, many patients with glaucoma still suffer from progressive visual disorders. Recently, ripasudil hydrochloride hydrate, a selective Rho-associated protein kinase inhibitor, was launched for the treatment of glaucoma. However, adverse events, such as conjunctival hyperemia, are often noted in clinical trials using healthy subjects. Therefore, we investigated the onset, offset, and kinetic changes of conjunctival hyperemia induced by ripasudil ophthalmic solution in patients with open-angle glaucoma or ocular hypertension who had already been treated with anti-glaucoma eye drops other than ripasudil. Conjunctival hyperemia was evaluated by both clinical grading by 3 ophthalmic physicians and pixel coverage of conjunctival blood vessels determined by conjunctival hyperemia-analyzing software. Conjunctival hyperemia appeared within 10 min post-instillation in most of the participants. Clinical grade and pixel coverage increased significantly 10 min post-instillation and then decreased. In most of the participants, hyperemia resolved within 2 h. Median conjunctival hyperemia offset was 90 min. A tendency of monotonic increase was observed between clinical grade and pixel coverage. Taken altogether, hyperemia induced by ripasudil was transient in glaucoma patients who had already been treated with anti-glaucoma eye drops other than ripasudil.
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http://dx.doi.org/10.1038/s41598-019-40255-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403378PMC
March 2019

Long-term Side Effects Including Blepharitis Leading to Discontinuation of Ripasudil.

J Glaucoma 2019 04;28(4):289-293

Departments of Ophthalmology.

Precis: Blepharitis was the most common side effect leading to discontinuation of ripasudil therapy. Prior allergic reactions to other topical glaucoma were found to be a risk factor for ripasudil-induced blepharitis.

Purpose: To report the incidence proportion of blepharitis and its relating factors due to long-term use of 0.4% riapasudil, a Rho-kinase inhibitor, in glaucoma patients of a clinical setting.

Patients And Methods: One hundred three eyes of 103 consecutive glaucoma patients who started ripasudil treatment between December 2014 and February 2017 at our institute, and who had a follow-up period of over 6 months were enrolled in this study. Incidence proportion, time required for recovery and risk factors associated with blepharitis and other side effects that led to discontinuation of ripasudil treatment were considered.

Results: The most frequently observed side effect was blepharitis (25.2%). The 12- and 24-month discontinuation rate due to blepharitis was 21.1%±8.2% and 34.6%±11.8% (average±SE), respectively (Kaplan-Meier analysis). Most patients recovered from blepharitis symptoms within 4 weeks, but 5 patients required over 8 weeks for recovery. Past history of allergic reactions to other topical glaucoma medication was significantly correlated with the manifestation of blepharitis (Cox proportional hazard model, P<0.007) while age, sex, intraocular pressure reduction rate, number of administered eye drops, history of systemic allergic diseases were not.

Conclusions: Blepharitis was the most common reason for discontinuation of ripasudil treatment. Although most cases were resolved spontaneously, prolonged blepharitis was observed in a few patients. A past history of allergic reaction to other glaucoma medication indicates a higher possibility of blepharitis with ripasudil use and warrants careful administration.
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http://dx.doi.org/10.1097/IJG.0000000000001203DOI Listing
April 2019

Development of conjunctivitis with a conjunctival proliferative lesion in a patient treated with dupilumab for atopic dermatitis.

Allergol Int 2019 Jul 2;68(3):383-384. Epub 2019 Feb 2.

Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University, Kochi, Japan.

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http://dx.doi.org/10.1016/j.alit.2018.12.012DOI Listing
July 2019

In vitro and in vivo performance of epinastine hydrochloride-releasing contact lenses.

PLoS One 2019 30;14(1):e0210362. Epub 2019 Jan 30.

Department of Ophthalmology, Nihon University, Itabashi, Tokyo, Japan.

A number of drug-releasing contact lenses are currently being studied to address issues inherent in eye drops as a drug delivery method. In this study, we developed epinastine hydrochloride-releasing daily soft contact lenses for treatment of allergic conjunctivitis and examined their in vitro and in vivo performance. Preformed soft contact lenses with/without ionic functional groups were soaked in a solution of epinastine hydrochloride in phosphate-buffered saline to prepare epinastine hydrochloride-releasing soft contact lenses. Among these contact lenses with different ionicities, anionic lenses demonstrated the maximum, relatively linear epinastine hydrochloride release, in vitro. The amount of epinastine hydrochloride release was directly proportional to the concentration of the epinastine hydrochloride solution used to prepare the contact lens. The epinastine hydrochloride-releasing anionic soft contact lens also demonstrated prolonged drug release and significantly greater efficacy compared with epinastine hydrochloride eye drops 12 h after treatment, in vivo. Further studies are required to determine the appropriate amount of epinastine hydrochloride to be contained in the anionic soft contact lenses.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210362PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6353132PMC
October 2019

Hyperemia Analysis Software for Assessment of Conjunctival Hyperemia Severity.

Curr Eye Res 2019 04 12;44(4):376-380. Epub 2018 Dec 12.

b Department of Ophthalmology , Kochi Medical School , Nankoku-city , Kochi , Japan.

Purpose: We developed a hyperemia analysis software, which can quantitatively assess the degree of conjunctival hyperemia, and evaluated the reproducibility and reliability of its percent coverage. In addition, we compared the clinical grading and the percent coverage to examine the applicability of the software analysis.

Methods: We took images of the temporal conjunctiva with slit lamp microscopes. We used our hyperemia analysis software to detect blood vessels in the region of interest using its image processing capabilities and obtained a ratio of the area occupied by blood vessels to the rest of the area. In addition, we used the clinical evaluation criteria of the Japanese guidelines for allergic conjunctival diseases 2017 to clinically grade the hyperemia in each eye. Nine evaluators examined the images and graded the severity of hyperemia into four stages. We looked for a statistical correlation between the results of the hyperemia analysis software and the clinical grading.

Results: The percent coverage of the blood vessels in the region of interest calculated by the hyperemia analysis software correlated with the arithmetic average of our clinical grading (r = 0.953; 95% CI, 0.8470340-0.9862136).

Conclusion: The percent coverage from our hyperemia analysis software reflects the clinical grading score, suggesting that our software can be used to obtain a detailed analysis of conjunctival hyperemia.
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http://dx.doi.org/10.1080/02713683.2018.1554153DOI Listing
April 2019

Periostin deletion suppresses late-phase response in mouse experimental allergic conjunctivitis.

Allergol Int 2019 Apr 9;68(2):233-239. Epub 2018 Nov 9.

Laboratory of Ocular Atopic Diseases, Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan. Electronic address:

Background: To investigate the potential roles of periostin (POSTN), an extracellular matrix preferentially expressed in Th2-skewed conditions in the pathophysiology of allergic conjunctivitis.

Methods: The roles of POSTN in ragweed-induced experimental allergic conjunctivitis (RW-EAC) were evaluated using both POSTN-knockout (KO) and congenic BALB/c wild-type mice. Histological analysis was carried out to enumerate eosinophils/basophils in the conjunctival tissue. Th2 cytokine expression was evaluated by quantitative polymerase chain reaction (Q-PCR), and microarray analysis was performed to elucidate genes differentially expressed in POSTN-KO and wild-type mice in the RW-EAC model.

Results: Upregulation of POSTN expression and eosinophil infiltration was observed in subconjunctival tissue of RW-EAC in the wild-type mice. The number of infiltrating eosinophils in the conjunctivae of RW-EAC was diminished in POSTN-KO mice compared to wild-type mice. Q-PCR analysis of conjunctival tissue showed induction of Th2 cytokine (Ccl5, Il4, Il5, Il13) expression in the RW-EAC and attenuated Ccl5, Il4, Il13 mRNA expression in the conjunctivae of the RW-EAC using POSTN-KO mice. Microarray analysis and immunohistochemical analysis showed diminished basophil marker (Mcpt8) expression and reduced numbers of infiltrating basophils in the conjunctivae of RW-EAC in POSTN-KO mice.

Conclusions: POSTN expression in conjunctival tissue plays an indispensable role in the late-phase reaction of the RW-EAC model by facilitating eosinophil/basophil infiltration and augmenting Th2 cytokine expression.
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http://dx.doi.org/10.1016/j.alit.2018.09.007DOI Listing
April 2019

Oral Immunotherapy for Allergic Conjunctivitis Using Transgenic Rice Expressing Hypoallergenic Antigens.

Cornea 2018 Nov;37 Suppl 1:S67-S73

Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi, Japan.

Pollinosis, or allergic conjunctivitis and rhinitis induced by pollen, is one of the most common diseases worldwide. In Japan, Japanese cedar (Cryptomeria japonica) pollinosis is a predominant allergic condition that affects more than one-third of all Japanese individuals. Pharmacological treatments of allergic conjunctivitis include administration of antiallergic eye drops containing an antihistamine or mast cell stabilizer. However, these topical treatments provide transient relief from symptoms. The only available curative treatment for allergic diseases is allergen-specific immunotherapy. Sublingual immunotherapy for pollinosis has been found to be effective for suppression of ocular and nasal symptoms, but patient compliance is low. Oral administration of staple foods engineered to express allergens is a possible means of delivering antigens for immunotherapy, and its convenience would be expected to improve compliance. With the aim of developing more convenient, effective, and safe immunotherapies for allergic diseases, we have generated rice-based edible vaccines expressing antigens derived from dust mites or pollen from Japanese cedar, birch, or ragweed. In this study, we summarize the results of our immunotherapy studies using transgenic rice. Oral immunotherapy with transgenic rice seeds containing hypoallergenic modified forms of Japanese cedar pollen antigens was effective for both preventing allergic conjunctivitis and suppressing established disease in mice. Oral administration of transgenic rice seeds is thus a promising approach to immunotherapy for conjunctivitis and rhinitis induced by Japanese cedar pollen.
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http://dx.doi.org/10.1097/ICO.0000000000001758DOI Listing
November 2018

Requirement of longer term antiviral therapy in patients with cytomegalovirus anterior uveitis with corneal endothelial cell damage.

Clin Ophthalmol 2018 25;12:1311-1316. Epub 2018 Jul 25.

Department of Ophthalmology and Visual Science, Kochi Medical School, Nankoku, Japan,

Background: The aim of the study was to investigate the efficacy of therapy in patients with cytomegalovirus (CMV) anterior uveitis.

Patients And Methods: We reviewed the records of patients with CMV anterior uveitis who attended our institution between October 2010 and December 2015 and who were confirmed to have CMV DNA in the aqueous humor by polymerase chain reaction analysis.

Results: Fourteen immunocompetent patients (10 men and 4 women, total of 17 eyes) were enrolled. The mean ± SD age at the onset of antiviral therapy was 63.1 ± 11.3 years (range, 44-87 years). CMV DNA was not detected in the aqueous humor of 3 patients on initial testing, but it was detected on subsequent analysis. All patients underwent systemic antiviral therapy. Among the patients who were followed up for more than 6 months after starting systemic antiviral therapy, systemic antiviral therapy was successfully terminated in all 4 patients without corneal endothelial loss but had to be continued because of disease recurrence on its termination in 5 of 8 patients (62.5%) with corneal endothelial damage ( = 0.038).

Conclusions: Patients with corneal endothelial cell loss are likely to require longer term antiviral therapy than those without endothelial damage. In addition, whereas definitive diagnosis of CMV anterior uveitis requires the detection of CMV DNA in aqueous humor by polymerase chain reaction, one-fifth of patients in the present study tested negative on initial examination.
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http://dx.doi.org/10.2147/OPTH.S164184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065568PMC
July 2018