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after treatment (Fig. 1f). While corneal topography by TMS-4 (Tomey, Nagoya, Japan) revealed no remarkable changes (Fig. 1c and g), pachymetric mapping by rotating Scheimpflug camera (Pentacam Oculus, Wetzlar, Germany) demonstrated a notable change in the corneal thickness of the lesion at 6 months after PDT, with the pachymetric value decreasing from approximately 600 to 400 μm (Fig. 1d and h).
Comments PDT seems to be the least invasive of all therapies currently available to selectively destroy neovascular networks, causing only minimal damage to the surrounding normal tissue. Animal studies have shown that PDT with verteporfin induces significant regression of corneal neovascularization without any observable changes in other anterior segment structures.3,4 A clinical trial has also demonstrated the usefulness of this method.2 However, that study revealed a high risk of PDT failure when the neovascularization network has expanded to cover a large area needing more than two irradiations. Fortunately, the affected area in our patient was small and could be covered by a single irradiation. The effect was maintained for at least 6 months. While the corneal topography remained essentially the same, the pachymetric mapping demonstrated a decrease in corneal thickness within the lesion. The amount of energy was 50 J/ cm2, which is reported to cause no significant histological changes due to the laser energy. Thus, one possible explanation for the observed corneal thinning is that after the PDT no exudates, including lipids, leaked from the vessel, and that the lipid deposits were gradually absorbed by the infiltrating cells. Although it remains unclear why no topographical changes were observed but corneal thinning was detected, we speculate that the thinning may not have been enough to cause changes in the ocular surface contour able to be detected as a topographical change. Another possible explanation is that pachymetric mapping by the rotating Scheimpflug camera is affected by the transparency of the cornea, which in the present case was decreased, resulting in inaccurate measurements and accounting for the discrepancy between the two analyses. Since in vivo confocal microscopic analysis can provide useful information concerning this phenomenon, we are planning to conduct such analyses in future cases. In conclusion, PDT is useful for treating corneal neovascularization in lipid keratopathy, particularly when small neovascular lesions can be covered by a single irradiation. The procedure can cause thinning of the cornea, which, however, seems to cause minimal topographic changes. Keywords: cornea, lipid keratopathy, neovascularization, PDT, photodynamic therapy Tsutomu Igarashi, Chiemi Yaguchi, Michinori Inage, Hisaharu Suzuki, and Hiroshi Takahashi Department of Ophthalmology, Nippon Medical School, Tokyo, Japan
Received: February 18, 2009 / Accepted: May 11, 2009 Correspondence to: Tsutomu Igarashi, Department of Ophthalmology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan e-mail:
[email protected] DOI 10.1007/s10384-009-0739-7
References 1. Caffery BE, Josephson JE. Corneal vascularization. Optom Clin 1995;4:19–29. 2. Yoon KC, You IC, Kang IS, et al. Photodynamic therapy with verteporfin for corneal neovascularization. Am J Ophthalmol 2007;144:390–395. 3. Holzer MP, Solomon KD, Vroman DT, et al. Photodynamic therapy with verteporfin in a rabbit model of corneal neovascularization. Invest Ophthalmol Vis Sci 2003;44:2954–2958. 4. Yoon KC, Ahn KY, Lee SE, et al. Experimental inhibition of corneal neovascularization by photodynamic therapy with verteporfin. Curr Eye Res 2006;31:215–224.
Cladosporium cladosporioides Keratomycosis: A Case Report Keratomycosis is a frequent cause of ocular morbidity and blindness. Filamentous fungi such as Fusarium and Aspergillus have been reported to be leading causes of keratomycosis in India1 and China.2 Keratomycosis caused by Cladosporium cladosporioides, a pigmented filamentous fungus, is very rare. We report a case of Cladosporium cladosporioides keratomycosis identified by polymerase chain reaction (PCR) and DNA typing.
Case Report A 37-year old man sustained a left corneal laceration in a car accident. The corneal laceration was sutured, and fourhourly topical administration of gatifloxacin (0.3%) and prednisolone (0.12%) was started. Two weeks later, the patient presented with pain OS. Best-corrected vision was 6/60 OS. Slit-lamp biomicroscopy revealed a superior paracentral epithelial defect measuring 1.3 mm in diameter and underlying stromal infiltrates with ill-defined margins. The patient was started on hourly topical ceftazidime (5%). Corneal scrapings for Gram staining and culture on day 3 were negative, and the patient was discharged with hourly topical ceftazidime. One week later, the patient complained of increased pain OS. Examination revealed a corneal epithelial defect measuring less than 1.0 mm in diameter and increased stromal infiltrates with feathery margins. An endothelial plaque and an inferior satellite lesion were also present. Reexamination of the corneal scraping cultures revealed velvety olivaceous brown colonies on Sabouraud’s medium. Microscopic findings showed long conidiophores that were
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not nodose, with terminal and lateral ramifications bearing branched smooth-walled, ellipsoidal conidia (Fig. 1). PCR was performed on a corneal scraping. The extracted genomic DNA was amplified using two different pairs of primers targeting internal transcribed spacer 1 (ITS1) and the 18S ribosomal RNA gene. The resulting sequence of 493 nucleotides was subjected to a homology search using the BLAST alignment program of the GenBank database (National Institutes of Health, Bethesda, MD, USA). The sequence was 100% identical to the Cladosporium cladosporioides gene, with a highest maximum score of 976 (GenBank accession number: EU 577236.1). The expected (E) value for the identity was 0.0, indicating that this result was nonrandom and highly statistically significant (Fig. 2). The isolate was thus identified as Cladosporium cladosporioides. Hourly topical pimaricin (natamycin) 5% was started. After 1 week, the patient received increased conjunctival injection which led to the reduction of pimaricin instillation to every 4 h. Within 2 months of the tapering of the pimaricin dosage, the corneal infiltration healed leaving a residual scar. The patient’s final best-corrected visual acuity in his left eye improved to 6/6.
Comments Cladosporium are pigmented fungi comprising of over 30 identifiable species. Cladosporium keratomycosis has been noted in various studies,1,3 but determination of the exact species has not been reported. Identification to the species level is important because the clinical prognosis with each species may vary. Only one case of corneal keratomycosis resulting from a dual infection of Cladosporium cladosporioides and Phialophora has been reported.4 To our knowledge, this is the first report of a case of purely Cladosporium cladosporioides keratomycosis. Clinical findings suggested a filamentous fungal infection. Pimaricin (a polyene antimycotic) was chosen, as it is
Figure 1. Photographs of the patient’s cornea and of a slide culture of a corneal scraping. Top: Photograph of the cornea at first presentation showing irregular stromal infiltrates and endothelial plaque. Bottom: Photograph of a slide culture of the corneal scraping stained with lactophenol cotton blue (original magnification ×400).
Figure 2. Nucleotide sequence of the polymerase chain reaction product amplified from the Cladosporium isolate with an ITS1/ ITS4 primer pair.
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fungicidal, effective against filamentous fungi, easily available, and produces an effective concentration in the corneal stroma on topical application. We believe our patient responded well to pimaricin because the infestation was by a single organism. The patient reported previously3 probably did not respond to pimaricin because of different drug–organism interactions caused by the dual infection causing that keratomycosis. In conclusion, Cladosporium cladosporioides is a very rare but treatable cause of keratomycosis. PCR for ITS1 and 18S ribosomal DNA typing were useful because they allowed identification of the organism and prompt initiation of appropriate therapy. Pimaricin monotherapy successfully resolved this keratomycosis caused by Cladosporium cladosporioides. Keywords: Cladosporium cladosporioides, keratomycosis, pimaricin, polymerase chain reaction Fiona L. M. Chew1, Visvaraja Subrayan1, Pei Pei Chong2, Meng Chuan Goh2, and Kee Peng Ng3 1 Department of Ophthalmology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 2 Department of Biomedical Sciences, Faculty of Medicine, Health and Sciences, University Putra Malaysia, Selangor, Malaysia; 3 Department of Medical Microbiology, University Malaya Medical Centre, Kuala Lumpur, Malaysia Received: December 14, 2008 / Accepted: June 9, 2009 Correspondence to: Fiona L. M. Chew, Department of Ophthalmology, Faculty of Medicine, University Malaya, Jalan Universiti, 50603 Kuala Lumpur, Malaysia e-mail:
[email protected] DOI 10.1007/s10384-009-0722-3
References 1. Srinivasan M, Gonzales CA, George C, et al. Epidemiology and aetiological diagnosis of corneal ulceration in Madurai, South India. Br J Ophthalmol 1997;81:965–971. 2. Sun X, Wang Z, Wang Z, Luo S, Li R. Ocular fungal isolates and susceptibility in northern China. Am J Ophthalmol 2007;143: 131–133. 3. Su CY, Lin CP, Kuo SL, Suen CY. Keratomycosis with an unusual clinical manifestation—a case report. Kaohsiung J Med Sci 1998;14: 311–314. 4. Polack FM, Siverio C, Bresky RH. Corneal chromomycosis: double infection by Phialophora verrucosa (Medlar) and Cladosporium cladosporioides (Frescenius). Ann Ophthalmol 1976;8:139–144.
A Case of Atypical Cogan’s Syndrome with Posterior Scleritis and Uveitis Cogan’s syndrome is a rare entity that is most common in young adult Caucasian patients and involves nonsyphilitic interstitial keratitis (IK), recurrent ocular inflammation, and Meniere-like episodes of vestibuloauditory symptoms that progress to complete deafness within 2 years.1–3 More recently, it has been recognized that Cogan’s syndrome can be classified into a typical form presenting with IK and an
atypical form with or without other severe inflammatory eye diseases.2 Here, we describe the clinical course of an elderly Japanese woman with posterior scleritis and uveitis associated with atypical Cogan’s syndrome.
Case Report A 59-year-old Japanese woman with a history of bilateral painful red eyes for 1 month underwent an initial examination in August 2004. She had no recent viral infection. On presentation, her best-corrected visual acuity was 20/30 OD and 20/20 OS. She had bilateral iritis. Funduscopic examination of the right eye showed a yellowish white elevated lesion in the inferior peripheral fundus. The left fundus appeared normal. Blood tests demonstrated an elevated white blood cell count of 11 200/mm3, an erythrocyte sedimentation rate of 88 mm/h, and C-reactive protein of 1.53 mg/dl, but the levels of antinuclear antibodies, serological tests for syphilis, fluorescent treponemal antibody absorption, and angiotensin-converting enzyme were all normal. B-scan ultrasound of the globes showed right posterior scleral thickening (Fig. 1a). Ocular pain continued despite local treatment with steroids. A slit-lamp examination revealed bilateral IK (Fig. 2a–d), and a fundus examination showed bilateral serous retinal detachment (SRD) in the inferior periphery. Intravenous (i.v.) methylprednisolone 1 g/day for 3 days was initiated for inflammatory eye disease, which initially showed a good response in reducing ocular pain, improving eye movement, and reducing SRD. In October 2004, the patient developed dizziness, acute bilateral hearing loss, right ocular pain, right visual loss, and bilateral worsening of vitreous opacity with a yellowish white elevated lesion in the inferior fundus (Fig. 1b). She was referred to the Department of Internal Medicine and Otolaryngology and diagnosed with sensorineural hearing loss associated with Cogan’s syndrome. The patient was retreated with methylprednisolone i.v. 1 g/day for 3 days for a presumed diagnosis of atypical Cogan’s syndrome with posterior scleritis. After the therapy, rapid improvement of her symptoms occurred with resolution of the posterior scleritis, but her hearing continued to fluctuate despite therapy. In July 2005, she complained of left eye pain during tapering of steroids, and recurrence of left posterior scleritis was retreated with methylprednisolone i.v. 1 g/day for 3 days. With the improvement of her symptoms, the steroids were slowly tapered, starting with an initial dose of 60 mg of oral prednisolone a day and tapering off the agent at a very slow pace of 5 mg over 8 weeks. By January 2006, she was completely deaf. At the 3-year follow-up, the dose of oral prednisolone was decreased to 15 mg/day and there has been no subsequent recurrence of symptoms.
Comments Differential diagnosis included atypical Cogan’s syndrome, sarcoidosis, tuberculosis, syphilis, Wegener’s granulomato-
