Effectiveness of laser pulsed irradiation for antimicrobial photodynamic therapy.

The aim of this study was to compare two types of light irradiation devices for antimicrobial photodynamic therapy (aPDT). A 660-nm light-emitting diode (LED) and a 665-nm laser diode (LD) were used for light irradiation, and 0.1 mg/L TONS 504, a cationic chlorin derivative, was used as the photosensitizer. We evaluated the light attenuation along the vertical and horizontal directions, temperature rise following light irradiation, and aPDT efficacy against Staphylococcus aureus under different conditions: TONS 504 only, light irradiation only, and TONS 504 with either LED (30 J/cm2) or LD light irradiation (continuous: 30 J/cm2; pulsed: 20 J/cm2 at 2/3 duty cycle, 10 J/cm2 at 1/3 duty cycle). Both LED and LD light intensities were inversely proportional to the square of the vertical distance from the irradiated area. Along the horizontal distance from the nadir of the light source, the LED light intensity attenuated according to the cosine quadrature law, while the LD light intensity did not attenuate within the measurable range. Following light irradiation, the temperature rise increased as the TONS 504 concentration increased in the order of pulsed LD < continuous LD < LED irradiation. aPDT with light irradiation only or TONS 504 only had no antimicrobial effect, while aPDT with TONS 504 under continuous or pulsed LD light irradiation provided approximately 3 log reduction at 30 J/cm2 and 20 J/cm2 and approximately 2 log reduction at 10 J/cm2. TONS 504-aPDT under pulsed LD light irradiation provided anti-microbial effect without significant temperature rise.

Case Report: Corneal Inlay Removal after Myofibroblast Detection under in Vivo Confocal Microscopy.

SIGNIFICANCE: Corneal inlays, one of the treatment options for presbyopia, are effective and safe, and various such devices have been developed. However, there have been cases of inlay removal due to complications or patient dissatisfaction. PURPOSE: The purpose of this study was to report a case of inlay removal due to corneal opacity after inlay implantation and the results of 5 years of follow-up. CASE REPORT: A 63-year-old man was referred to our hospital with visual disturbance and double vision in his left eye. Two years before presentation at our hospital, he had undergone bilateral laser in situ keratomileusis with corneal inlay implantation in the left eye at another clinic. Slit-lamp examinations showed paracentral corneal opacity. The patient was treated with tranilast eye drops for 18 months, with no progression of symptoms. However, 6 months after stopping the eye drop treatment, the opacity recurred, and vision acuity decreased, along with the formation of myofibroblasts around the inlay, as revealed by in vivo confocal microscopy. Consequently, the inlay was removed at the previous clinic. During the subsequent 5-year follow-up period, ophthalmic examination revealed reduced corneal opacity, although visual acuity did not change; moreover, no myofibroblast was found. CONCLUSIONS: Corneal inlays can sometimes cause complications. In this case, the patient experienced corneal fibrosis and associated vision loss. In vivo confocal microscopy detected myofibroblasts that cause corneal stromal fibrosis; thus, the removal was decided to avoid fibrosis progression.

Synergistic effect of TONS504-mediated photodynamic antimicrobial chemotherapy and additives widely contained in ophthalmic solutions: benzalkonium chloride and ethylenediaminetetraacetic acid.

TONS504 (C51H58N8O5I2), a chlorine derivative, effectively generates singlet oxygen by light activation and exhibits photodynamic antimicrobial effects (PAEs) on various pathogens. However, this photosensitizer has some limitations: a high tendency to self-aggregate and a relatively weak PAE for Gram-negative bacteria compared with Gram-positive bacteria. To overcome these limitations, the present study investigated the synergistic effects of the PAE of TONS504 and two additives commonly contained in ophthalmic solutions: benzalkonium chloride (BAC) or ethylenediaminetetraacetic acid (EDTA). Staphylococcus aureus and Pseudomonas aeruginosa were exposed to TONS504 and/or each additive. Photodynamic antimicrobial chemotherapy was performed with light irradiation centered at a wavelength of 665 nm with a total light energy of 30 J/cm2. Following incubation, the number of colonies formed was counted. Additionally, we examined the inhibitory effects of the additives on TONS504 self-aggregation by observing its absorption spectrum. Consequently, the PAEs of TONS504 on S. aureus were enhanced by both additives, and BAC displayed stronger synergistic effects on the bacteria than EDTA. By contrast, only EDTA increased the PAE on P. aeruginosa. The peak of the TONS504 absorption spectrum shifted to a longer wave length and the absorbance increased in the presence of BAC, suggesting that BAC inhibited the self-aggregation of the photosensitizer. In conclusion, the combination of BAC or EDTA and TONS504-mediated photodynamic antimicrobial chemotherapy exhibits a synergistic antimicrobial effect on S. aureus and P. aeruginosa. The optimal additive to enhance the PAE may differ between bacterial strains.

Vernal keratoconjunctivitis with a limbal mass lesion developing independently of severe papillae formation at the tarsal conjunctiva: a case report.

BACKGROUND: A hypertrophic limbal mass lesion is an uncommon finding of vernal keratoconjunctivitis; it normally occurs in eyes with severe papillae formation in the tarsal conjunctiva. We present a case with a limbal mass lesion in a patient with relatively mild allergic findings in the tarsal conjunctiva. CASE PRESENTATION: A 12-year-old Japanese boy displaying allergic conjunctivitis presented with a mass lesion at the inferior limbus in the left eye. Relatively mild papillae formation was found on the tarsal conjunctiva in both eyes. We diagnosed that the mass lesion resulted from limbal vernal keratoconjunctivitis and resected it for therapeutic purposes. Histopathological examination showed that eosinophils, lymphocytes, and fibroblasts were present in the subepithelial lesion and the substantia propria of the mass lesion. Immunohistochemical staining detected diffuse and rich infiltration of CD3-positive T lymphocytes and a relatively small number of CD20-positive B lymphocytes and CD138-positive plasma cells that tended to aggregate. The histopathologic features suggested that the limbal mass lesion had similar structures to the papillae at the tarsal conjunctiva of vernal keratoconjunctivitis. CONCLUSION: The limbal mass lesion as a finding of vernal keratoconjunctivitis can occur even if the papillae formation at the patient's tarsal conjunctiva is mild.

Technical Report: Automatic Measurement of Corneal Nerve Fiber Area Using Versatile Software.

SIGNIFICANCE: In vivo confocal microscopy has become a popular method to observe the details of corneal structures. We consider the area of corneal structures to be a versatile index and have measured the areas of various corneal structures using a commercially available software. PURPOSE: This study aimed to evaluate the accuracy of software used to measure the corneal nerve fiber area. METHODS: The corneal structures of 11 healthy volunteers were visualized using in vivo confocal microscopy. The image that most clearly depicted the corneal nerve fibers of each participant was selected for analysis. The corneal nerve fiber area was automatically measured by the software. An experienced ophthalmologist then manually measured the corneal nerve fiber area in each image assessed by the software. The Pearson correlation test was used to determine the correlation coefficient between the corneal nerve fiber areas measured automatically and those measured manually. The correlation between the corneal nerve fiber area and the participant's age was also evaluated. RESULTS: A strong correlation was found between the corneal nerve fiber area measured automatically and the corneal nerve fiber area measured manually ( r = 0.98, P = 2.4 × 10 -7 ). The corneal nerve fiber area was not correlated with participant age, regardless of whether the area was measured automatically ( r = -0.26, P = .44) or manually ( r = -0.13, P = .71). CONCLUSIONS: The software used in this study automatically measures the corneal nerve fiber area with accuracy similar to that of manual measurement by an experienced ophthalmologist. This software has potential for use in quantifying the areas of various corneal structures.

Efficacy of Photodynamic Anti-Microbial Chemotherapy for Acanthamoeba Keratitis In Vivo.

BACKGROUND AND OBJECTIVES: Acanthamoeba keratitis is a sight-threatening infectious disease that is difficult to treat. The aim of this study was to evaluate TONS504 (cationic chlorin derivative photosensitizer)-mediated photodynamic antimicrobial chemotherapy (PACT) in vivo as a potential treatment for Acanthamoeba keratitis. STUDY DESIGN/MATERIALS AND METHODS: Acanthamoeba keratitis was induced by soft contact lenses incubated with 1 × 105 /ml Acanthamoeba castellanii, which were placed over debrided corneas with temporary tarsorrhaphy. Thirty-eight male Japanese white rabbits were randomly divided into three groups (normal eye, no treatment, and treatment groups). TONS504 was administered as eye drops at 1 mg/ml, followed by light-emitting diode irradiation after the establishment of keratitis at 7 days after infectious contact lens exposure. All animals were evaluated under a slit-lamp microscope every 3 days for 6 days after the treatment. Clinical scores based on corneal epithelial defects detected by fluorescein staining, stromal opacity edema, and vascular infiltration into the cornea were determined. After 6 days, the eyes were enucleated for histopathological analysis. RESULTS: Clinical signs of infection in the treatment group were markedly reduced for up to 6 days after treatment. Histopathology showed a regular arrangement of stromal fibers and a small number of inflammatory cells in 58% of the corneas. However, 42% of corneas in the treatment group showed infiltrating neutrophils and irregular alignment of stromal collagen fibers. CONCLUSIONS: Our TONS504-PACT achieved complete recovery from keratitis in 58% of the rabbit models. Further studies are required to determine the conditions for the maximal effectiveness of our TONS504-PACT for Acanthamoeba keratitis. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Antifungal efficacy of photodynamic therapy with TONS 504 for pathogenic filamentous fungi.

The pathogenic filamentous fungi Fusarium solani (F. solani) and Aspergillus fumigatus (A. fumigatus) are common causes of fungal keratitis. We have here evaluated the antifungal efficacy of photodynamic antimicrobial chemotherapy (PACT) with the novel chlorin derivative TONS 504 and a light-emitting diode (LED) with a wavelength of 660 nm for these fungal species. Isolated fungal spores were irradiated at LED energies of 10, 20, or 30 J/cm2 in the presence of TONS 504 at concentrations of 1 or 10 mg/L. As a control, spores were exposed to TONS 504 or LED radiation alone. The treated spores were then cultured on potato dextrose agar plates at 25 °C for 3 to 4 days before determination of colony formation as a measure of viability. Fungal growth was inhibited in a manner dependent on both LED energy and TONS 504 concentration. The inhibitory effect on F. solani was complete with TONS 504 at a concentration of 1 mg/L and LED irradiation at 30 J/cm2 as well as at a TONS 504 concentration of 10 mg/L and LED irradiation at 10, 20, or 30 J/cm2. In contrast, that on A. fumigatus was only partial at a TONS 504 concentration of 10 mg/L and LED irradiation at 20 or 30 J/cm2. The antifungal effect of PACT on A. fumigatus was thus inferior to that on F. solani. PACT with TONS 504 and an LED thus warrants further evaluation with regard to its potential effectiveness for the treatment of infectious fungal keratitis.

Time-dependent antimicrobial effect of photodynamic therapy with TONS 504 on Pseudomonas aeruginosa.

Pseudomonas aeruginosa (P. aeruginosa) is a major cause of infectious keratitis, which itself is a major cause of blindness worldwide. We have now evaluated the time-dependent effectiveness of photodynamic antimicrobial chemotherapy (PACT) with the chlorin derivative TONS 504 and a light-emitting diode (LED) on P. aeruginosa in vitro. PACT with TONS 504 (10 mg/L) and irradiation (30 J/m2) by an LED device that delivers light centered on a wavelength of 660 nm was applied to 1 × 106 colony-forming units of P. aeruginosa in liquid medium. The bacteria were then cultured at 37 °C for various times before assay of viability by determination of colony formation on agar plates. The effect of a second irradiation at 3 h after the initial LED exposure was also examined. Bacterial growth was markedly inhibited between 3 and 9 h after PACT with TONS 504, with the maximal effect being apparent at 3 h. Furthermore, a second exposure to LED irradiation at 3 h after the first treatment enhanced the inhibitory effect on bacterial growth. PACT with TONS 504 thus inhibited the growth of P. aeruginosa in a time-dependent manner, and an additional irradiation exposure applied 3 h after the first LED treatment greatly increased the effectiveness of PACT. This antibacterial system thus warrants further evaluation with regard to its potential effectiveness for the treatment of infectious keratitis.

Comparison of semi-automated center-dot and fully automated endothelial cell analyses from specular microscopy images.

PURPOSE: To evaluate two specular microscopy analysis methods across different endothelial cell densities (ECDs). METHODS: Endothelial images of one eye from each of 45 patients were taken by using three different specular microscopes (three replicates each). To determine the consistency of the center-dot method, we compared SP-6000 and SP-2000P images. CME-530 and SP-6000 images were compared to assess the consistency of the fully automated method. The SP-6000 images from the two methods were compared. Intraclass correlation coefficients (ICCs) for the three measurements were calculated, and parametric multiple comparisons tests and Bland-Altman analysis were performed. RESULTS: The ECD mean value was 2425 ± 883 (range 516-3707) cells/mm2. ICC values were > 0.9 for all three microscopes for ECD, but the coefficients of variation (CVs) were 0.3-0.6. For ECD measurements, Bland-Altman analysis revealed that the mean difference was 42 cells/mm2 between the SP-2000P and SP-6000 for the center-dot method; 57 cells/mm2 between the SP-6000 measurements from both methods; and -5 cells/mm2 between the SP-6000 and CME-530 for the fully automated method (95% limits of agreement: - 201 to 284 cell/mm2, - 410 to 522 cells/mm2, and - 327 to 318 cells/mm2, respectively). For CV measurements, the mean differences were - 3, - 12, and 13% (95% limits of agreement - 18 to 11, - 26 to 2, and - 5 to 32%, respectively). CONCLUSIONS: Despite using three replicate measurements, the precision of the center-dot method with the SP-2000P and SP-6000 software was only ± 10% for ECD data and was even worse for the fully automated method. CLINICAL TRIAL REGISTRATION: Japan Clinical Trials Register ( http://www.umin.ac.jp/ctr/index/htm9 ) number UMIN 000015236.

The Japan Cornea Society Survey of the Current Status of Corneal and Conjunctival Disorders Due to Systemic Antitumor Drugs.

Purpose: To investigate the current status of corneal and conjunctival disorders due to antitumor drugs in Japan. Methods: Questionnaires on corneal and conjunctival disorders due to antitumor drugs were sent to members of the Japan Cornea Society, and data on patients' background, clinical findings, treatment and prognosis of cases between January 2009 and December 2011 were collected and analyzed. Results: Out of all 221 cases from 66 facilities, TS-1Ⓡ had been administered in 210 cases (95.0%). Corneal findings were noted in 192 cases (86.9%), including 161cases (72.9%) of superficial punctate keratopathy, 55 cases (24.9%) of epithelial crack line, 38 cases (17.2%) of sheet-like epithelial abnormality, and 15 cases (6.8%) of corneal erosion. Conjunctival and ciliary findings were observed in 49 cases (22.2%). Lacrimal obstruction and constriction were found in 81cases (36.7%). Logistic regression analyses revealed the discontinuation and switching of antitumor drugs as the significant factor of good prognosis of clinical signs and visual acuity in cases with TS-1Ⓡ administration. Conclusions: Although corneal and conjunctival disorders due to antitumor drugs, especially TS-1Ⓡ, are important adverse effects, the only effective treatment at this time is the discontinuation and switching of antitumor drugs. Future prospective studies are needed to elucidate pathogenesis, aiming to the prediction and prevention of the occurrence.

Inactivation of acyclovir-sensitive and -resistant strains of herpes simplex virus type 1 in vitro by photodynamic antimicrobial chemotherapy.

PURPOSE: To evaluate the efficacy of photodynamic antimicrobial chemotherapy (PACT) with the new porphyrin derivative TONS 504 and a light-emitting diode (LED) against acyclovir (ACV)-sensitive and -resistant herpes simplex virus type 1 (HSV-1). METHODS: Human FL cells infected with the viral strains were subjected to PACT with TONS 504 at various concentrations (0.01 to 10 mg/l) and irradiation at various light energies (10 to 30 J/cm(2)) and were then incubated for 24 h before analysis. RESULTS: Immunocytofluorescence analysis with antibodies to HSV-1 revealed that PACT eliminated HSV-1 and ACV-resistant HSV-1 in a manner dependent on the TONS 504 concentration and light energy. Complete eradication of both viruses was apparent at a TONS 504 concentration of 10 mg/l and light energy of 10 to 30 J/cm(2) as well as at a TONS 504 concentration of 1 mg/l and light energy of 20 or 30 J/cm(2). No antiviral effect was apparent with TONS 504 in the absence of irradiation or with irradiation in the absence of TONS 504. Staining of cell nuclei with 4', 6-diamidino-2-phenylindole revealed no apparent cytotoxicity of the PACT system, a finding that was confirmed by the system's failure to induce the release of lactate dehydrogenase from the host cells. CONCLUSIONS: We conclude that our PACT system based on TONS 504 and an LED is effective for eliminating HSV-1 and ACV-resistant HSV-1 without a harmful effect on host cells.

Antimicrobial action from a novel porphyrin derivative in photodynamic antimicrobial chemotherapy in vitro.

Efforts to identify improved treatments for corneal infection include the development of photodynamic antimicrobial chemotherapy (PACT). We evaluated the antimicrobial effect of PACT with a novel porphyrin derivative, TONS 504, and a novel light system on methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA). Bacteria were irradiated with a light-emitting diode (LED) at energies of 10, 20, or 30 J/cm(2) in the presence of various concentrations of TONS 504. Bacterial viability was assessed at 30 min and 24 h after irradiation by determination of colony formation on agar plates. PACT inhibited the growth of both MSSA and MRSA as early as 30 min after light exposure. Complete inhibition of bacterial growth was apparent at 24 h after irradiation at a TONS 504 concentration of 1 mg/L and LED energies of ≥10 J/cm(2) or a TONS 504 concentration of 0.5 mg/L and LED energies of ≥20 J/cm(2) for MSSA, and at a TONS 504 concentration of 10 mg/L and LED energies of ≥10 J/cm(2) or of a TONS 504 concentration of 1 mg/L and LED energies of ≥20 J/cm(2) for MRSA. Bacterial growth was unaffected by TONS 504 in the absence of irradiation or by irradiation in the absence of TONS 504. Our results thus demonstrate the antimicrobial efficacy of PACT with TONS 504 and a LED against both MSSA and MRSA in vitro, and they therefore provide a basis for further investigation of this system as a potential treatment for corneal infection.

Rapid Corneal Calcification Following Endothelial Keratoplasty: A Case Report.

Corneal calcification typically progresses slowly but can occasionally advance rapidly. This report details severe stromal calcification following repeat Descemet's stripping automated endothelial keratoplasty (DSAEK) in a 75-year-old patient with diabetes, hypertension, and prior ocular surgeries, including cataract surgery, intraocular lens extraction with suturing, and trabeculectomy. Persistent epithelial defects after the surgery led to rapid central stromal calcification within four weeks, significantly reducing visual acuity. Management included switching from betamethasone sodium phosphate to fluorometholone, facilitating complete epithelial recovery within two months. However, persistent stromal opacity necessitated a subsequent penetrating keratoplasty. Infrared absorption spectrophotometry identified calcium phosphate as the primary component of the calcification. This case highlights the importance of vigilant monitoring and proactive management of epithelial defects to prevent rapid calcification following endothelial keratoplasty.

Blocking Air in the Filtering Bleb: Effects on Graft Adhesion After Descemet's Stripping Automated Endothelial Keratoplasty.

BACKGROUND: To evaluate the outcome of Descemet's stripping automated endothelial keratoplasty (DSAEK) with "blocking air" in the filtering bleb in patients with previous trabeculectomy. METHODS: In total, 299 eyes in 283 patients who underwent DSAEK were retrospectively reviewed. Endothelial graft adhesion, intraocular pressure (IOP), and air volume in the anterior chamber with (group A) or without (group B) a filtering bleb were compared between the groups. Group A was divided into two subgroups according to the presence (group A1) or absence (group A2) of air in the filtering bleb; the same three factors were compared between the subgroups. RESULTS: The graft detachment rate was significantly higher in group A (14.3%) than in group B (6.5%) (p = 0.04). IOP was significantly lower in group A than in group B before surgery (p = 0.01), at the end of surgery (p = 0.04), at three hours (p < 0.001), and one week postoperatively (p = 0.02). The graft detachment rate did not significantly differ between groups A1 and A2. There were no differences in IOP at each follow-up time, whereas there was a statistically significant increase in IOP from the preoperative measurement to the end of surgery in group A1 (21.0±7.0 mmHg) compared with group A2 (14.2±8.6 mmHg) (p = 0.02). CONCLUSIONS: The presence of blocking air in the filtering bleb helps ensure increased IOP during the early postoperative period but had no significant effect on graft detachment rates.

Matrix metalloproteinase and cytokine expression in Tenon fibroblasts during scar formation after glaucoma filtration or implant surgery in rats.

Failure of surgery for glaucoma is usually due to post-surgical scarring (fibrosis), a process in which fibroblasts play a prominent role. We investigated the molecular mechanisms of such scarring by examining the expression of matrix metalloproteinases and cytokines in Tenon fibroblasts isolated from rats after glaucoma surgery. Filtration surgery was performed in one eye and implant surgery in the other; and Tenon fibroblasts were isolated from the tissue surrounding the bleb after surgery. The cells were cultured and examined for the expression of matrix metalloproteinases (MMPs) by reverse transcription-polymerase chain reaction, immunoblot and gelatin zymographic analyses. Culture supernatants were also assayed for cytokines with a multiplex array. The amounts of MMP-1 and MMP-3 mRNAs and proteins were greater in cells isolated after implant surgery than in those isolated after filtration surgery, with the progression of scar formation being more complete after the former surgery. The secretion of interleukin-6 (IL-6) by cells isolated after filtration surgery was greater than that for cells isolated after implant surgery. Depletion of IL-6 by RNA interference in cells isolated after filtration surgery increased the expression of MMP-1 and MMP-3 in these cells. These results thus suggest that the expression of MMP-1 and MMP-3 in Tenon fibroblasts is regulated by IL-6 during, and may play an important role in, scar formation after glaucoma surgery.

Efficacy of azithromycin hydrate ophthalmic solution for treatment of internal hordeolum and meibomitis with or without phlyctenular keratitis.

PURPOSE: To evaluate the efficacy of azithromycin hydrate ophthalmic solution for the treatment of internal hordeolum and meibomitis with or without phlyctenular keratitis. STUDY DESIGN: Retrospective study. METHODS: Patients diagnosed with internal hordeolum or meibomitis were prescribed azithromycin hydrate ophthalmic solution twice daily for 2 days and then once daily for 12 days. Depending on the presence of meibomitis-related keratoconjunctivitis (MRKC), we further divided the patients with meibomitis into three subgroups: meibomitis alone (non-MRKC group), meibomitis with non-phlyctenular MRKC (non-phlyctenular group), and meibomitis with phlyctenular MRKC (phlyctenular group). Inflammatory findings (eyelid redness and conjunctival hyperemia) were scored before and after treatment. Some patients also underwent culture testing fluids discharged by the meibomian gland orifices. RESULTS: Three patients (3 eyes) had internal hordeolum and 16 patients (16 eyes) had meibomitis. After treatment, the inflammatory findings disappeared in all eyes with internal hordeolum. Among the patients with meibomitis, three eyes were in the non-MRKC, six in the non-phlyctenular, and seven in the phlyctenular group. The inflammatory findings were significantly improved only in the phlyctenular group. Among seven eyes with positive culture results, Cutibacterium acnes was detected in five, and treatment improved the inflammatory findings in all of these eyes. CONCLUSION: Azithromycin hydrate ophthalmic solution is effective for the treatment of inflammatory meibomian gland diseases, including internal hordeolum and meibomitis. In particular, the agent is highly efficient in patients with phlyctenular MRKC.

Refractory Fungal Keratitis Caused by Acrophialophora fusispora: A Case Report and Literature Review.

Acrophialophora fusispora is a filamentous fungus that is found in soil and rarely infects humans. We herein report the first case of fungal keratitis caused by A. fusispora in Japan and present a review of the literature on human infections with Acrophialophora species. A 62-year-old Japanese male on immunosuppressive therapy developed fungal keratitis after the removal of a corneal foreign body from his left eye. Voriconazole eye drops and systemic therapy for post-traumatic fungal keratitis did not resolve the infection, and the patient required a therapeutic corneal transplant. The isolate was identified as A. fusispora based on the nucleotide sequence of the internal transcribed spacer region. In a drug susceptibility test, the minimum inhibitory concentration of voriconazole was 0.5 µg/mL. Based on this case and previous cases from the literature review, fungal keratitis caused by A. fusispora is often refractory.

Inflammatory Cells and Lipid Deposits Detected by in Vivo Confocal Microscopy in Brimonidine Tartrate Ophthalmic Solution-Related Corneal Disorders: A Case Series.

We reviewed the medical charts of five patients diagnosed with brimonidine tartrate (BT)-related corneal disorders. A fan-shaped corneal opacity was present in four patients and limbal corneal infiltrations were present in one patient. In vivo confocal microscopy revealed dendritic cells and lipid deposits in the fan-shaped opacity as well as neutrophils in limbal infiltrations. BT instillation was discontinued and topical administration of a corticosteroid was initiated for all patients. The limbal infiltrations improved after BT discontinuation. Conversely, the fan-shaped opacity remained in all affected patients. After a fan-shaped opacity has developed in a patient with a BT-related corneal disorder, the lesion is difficult to resolve. However, limbal infiltrations respond well to treatment. Therefore, BT should be discontinued and anti-inflammatory treatment initiated before a fan-shaped opacity forms.

Usefulness of smear microscopy for therapeutic decision-making in patients with infectious keratitis.

PURPOSE: To determine the usefulness of smears in the diagnosis of infectious keratitis by comparing smears and 2 different culture methods. STUDY DESIGN: Retrospective, observational study. METHODS: The foci of 73 patients diagnosed with infectious keratitis at Hiroshima University Hospital between July 2011 and September 2015 were abraded, and smear microscopy and culturing were performed. The microorganism detection rates and other parameters were compared. RESULTS: Microorganisms were detected in 47 of 73 specimens. Microorganisms were identified in 32 of 69 cases cultured on plain medium (detection rate, 46.4%) compared with 22 of 61 cases cultured on swab transport medium (detection rate, 36.1%). There was no significant difference in the microbial detection rate between the plain medium method and the swab transport medium method (P = 0.23). Smear microscopy and culture findings were concordant in 21 (28.8%) cases, and different microorganisms were detected in 9 cases. In 17 cases, the culture was negative, despite the presence of microorganisms on smear microscopy, and in 7 cases, the culture was positive, despite the absence of microorganisms on smear microscopy. The positivity rate of microbial detection was significantly higher when no antimicrobial agents had been administered previously (odds ratio 7.50, P = 0.017). CONCLUSION: Smear microscopy of abrasions from lesions is useful for the initiation of treatment for infectious keratitis. However, culture studies should be conducted at the same time to confirm antimicrobial sensitivity. If possible, smear microscopy should be performed before the initiation of antimicrobial therapy.

Corneal Copper Deposition Secondary to Monoclonal Gammopathy in a Patient With Chronic Lymphocytic Leukemia: A Case Report.

Hypercupremia-induced corneal copper deposition secondary to monoclonal gammopathy is rare and shows a characteristic corneal opacity quite different from other causes of hypercupremia, such as Wilson's disease. This report describes a case of corneal copper deposition in a patient with monoclonal gammopathy associated with chronic lymphocytic leukemia. An 84-year-old man with slowly progressive corneal opacity was referred to our hospital. The corneal opacity was present at least five years ago. The patient's best-corrected visual acuity was 20/25 OU (in both eyes) at the initial visit to our hospital. Slit-lamp examination and anterior segment optical coherence tomography revealed bilateral brown-colored opacity localized to deep layers of the central cornea. In vivo confocal microscopy (IVCM) showed indistinct corneal stromal cells in the deep layer and endothelial cells. The possible differential diagnoses were corneal dystrophy and Wilson's disease, but the color, shape, or site of corneal opacity was inconsistent with the disease. As the patient had a history of chronic lymphocytic leukemia, which is often associated with monoclonal gammopathy, we suspected that the corneal opacity was copper deposition in association with the hematologic diseases. Laboratory examinations showed elevated serum copper and normal ceruloplasmin. Serum protein electrophoresis revealed significantly high IgG levels with depression of IgA, IgE, and IgM. These results supported our diagnosis. Followingly, we consulted the patient's attending hematologist, and the doctor initiated treatment for hypercupremia. In conclusion, hypercupremia secondary to monoclonal gammopathy should be considered a possible cause of central brown-colored corneal opacity.