Publications by authors named "Ryoji Yamakawa"

31 Publications

Management of Recurrent Pterygium with Severe Symblepharon Using Mitomycin C, Double Amniotic Membrane Transplantation, Cryopreserved Limbal Allograft, and a Conjunctival Flap.

Int Med Case Rep J 2020 21;13:201-209. Epub 2020 May 21.

Department of Ophthalmology, Kurume University School of Medicine, Fukuoka, Japan.

Purpose: The aim of this study was to evaluate the clinical outcomes of management of recurrent pterygium with severe symblepharon using mitomycin C, double amniotic membrane transplantation, cryopreserved limbal allograft, and a conjunctival flap.

Patients And Methods: This retrospective case series included 10 eyes of 10 patients with recurrent pterygium with severe symblepharon. Eight patients have diplopia in primary gaze. All patients underwent pterygium excision, application of mitomycin C (MMC), double amniotic membrane transplantation (AMT), cryopreserved limbal allograft (CLA) transplantation, and placement of a conjunctival flap. Outcome measures were visual acuity, astigmatism, and recurrence. Recurrence was defined as the presence of fibrovascular proliferative tissue crossing the limbus.

Results: The patients' mean age was 73.8 years. The mean follow-up period was 3.0 years. The mean preoperative and postoperative best-corrected visual acuities (logMAR conversion) were 0.43 and 0.30, respectively. The mean preoperative and postoperative astigmatism were -3.89 diopters and -1.54 diopters, respectively, and there was a significant difference. No recurrence occurred in any of the eyes. Symblepharon was released in all eyes. Diplopia in primary gaze was resolved in all eyes.

Conclusion: Management of recurrent pterygium with severe symblepharon using MMC, double AMT, CLA, and a conjunctival flap was an effective treatment.
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http://dx.doi.org/10.2147/IMCRJ.S245256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247734PMC
May 2020

Macular ganglion cell complex measurement in bilateral retrobulbar optic neuropathy without a relative afferent pupillary defect.

Int Med Case Rep J 2018 25;11:145-150. Epub 2018 Jun 25.

Department of Ophthalmology, Kurume University School of Medicine, Kurume, Japan,

Purpose: This study aimed to demonstrate the clinical usefulness of measuring the macular ganglion cell complex (GCC) for the early detection of axonal loss in eyes with bilateral retrobulbar optic neuropathies.

Patients And Methods: We retrospectively reviewed the medical records of three patients with bilateral toxic, ischemic, or infiltrative retrobulbar optic neuropathy.

Results: No relative afferent pupillary defect was detected in any patients. The results of the fundus examinations were unremarkable at the initial presentation except for slight optic disk pallor in the right eye of Case 3. Magnetic resonance imaging showed no abnormal findings in Cases 1 and 2. Measurement of the macular GCC clarified the presence of axonal loss in all three cases with diagnostic uncertainty. Although reduction in the macular GCC thickness was not observed initially in Case 2, it became evident later when both optic disks still appeared normal.

Conclusion: A reduction in the macular GCC thickness seemed to precede the appearance of optic disk pallor and occurs regardless of toxic, ischemic, or infiltrative retrobulbar optic neuropathy. The current case series suggested that measurement of the macular GCC facilitated early differentiation between bilateral retrobulbar optic neuropathy and nonorganic visual loss, which can otherwise be challenging in some cases.
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http://dx.doi.org/10.2147/IMCRJ.S160417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6022815PMC
June 2018

Recurrent pterygium treatment using mitomycin C, double amniotic membrane transplantation, and a large conjunctival flap.

Int Med Case Rep J 2018 7;11:47-52. Epub 2018 Mar 7.

Department of Ophthalmology, Kurume University School of Medicine, Fukuoka, Japan.

Purpose: The aim of this study was to evaluate the clinical outcomes of surgery for recurrent pterygia using mitomycin C (MMC), double amniotic membrane transplantation (AMT), and a large conjunctival flap.

Patients And Methods: This retrospective case series included 31 eyes in 31 patients with recurrent pterygia. All patients underwent pterygium excision, application of MMC, double AMT, and placement of a large conjunctival flap. Outcome measures were visual acuity, astigmatism, and recurrence. Recurrence was defined as the presence of fibrovascular proliferative tissue crossing the limbus.

Results: The patients' mean age was 68.2 years. The mean follow-up period was 3.6 years. The mean preoperative and postoperative best-corrected visual acuities (logMAR conversion) were 0.23 and 0.13, respectively. There was a significant difference between the mean preoperative (-3.85 D) and postoperative (-2.22 D) astigmatism. The recurrence rate was 3.2% (1/31 cases).

Conclusion: Surgical pterygium excision with application of MMC, double AMT, and placement of a large conjunctival flap was an effective treatment for recurrent pterygia.
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http://dx.doi.org/10.2147/IMCRJ.S150969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848662PMC
March 2018

Regulator of G-protein signaling 5 enhances portal vein invasion in hepatocellular carcinoma.

Oncol Lett 2018 Feb 23;15(2):1763-1770. Epub 2017 Nov 23.

Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.

Portal vein invasion (PVI) is a major prognostic factor in hepatocellular carcinoma (HCC). The aim of the present study was to identify molecules that regulate PVI. Sections of cancerous tissue, paired noncancerous tissue and the PVI area were collected from 3 frozen HCC sections, using laser microdissection. The present study focused on 3 upregulated molecules, integrin β3 (ITGB3), secreted phosphoprotein 1 (SPP1) and regulator of G-protein signaling 5 (RGS5), and 2 molecules that were downregulated in PVI tissue compared with cancer tissue, metallothionein 1G (MT1G) and metallothionein 1H (MT1H), as determined by cDNA microarray analysis. Reverse transcription-quantitative polymerase chain reaction analysis of 32 HCC cases revealed that RGS5 mRNA levels were significantly increased and MT1 G and MT1H mRNA levels were significantly decreased in cancerous tissue compared with noncancerous tissue. However, there was no significant difference in ITGB3 and SPP1 expression. There were no significant differences between the expression of these molecules and any clinicopathologic factors, including PVI. Immunohistochemical staining for RGS5 in 60 HCC cases demonstrated that RGS5 protein levels were higher in cancerous tissue compared with paired noncancerous tissue in 63.3% of HCC cases. Furthermore, high expression of RGS5 in cancerous tissue was significantly associated with PVI and tended to be associated with intrahepatic metastasis. Confluent multinodular type was significantly more frequent in cases with high expression of RGS5 in the cancerous tissue. Therefore, RGS5 may be a useful prognostic biomarker as well as a potential target of molecular therapy to treat HCC.
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http://dx.doi.org/10.3892/ol.2017.7474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774499PMC
February 2018

MACULAR HOLE FORMATION AFTER PARS PLANA VITRECTOMY FOR PRIMARY VITREORETINAL LYMPHOMA.

Retin Cases Brief Rep 2020 ;14(3):243-246

Department of Ophthalmology, Kurume University School of Medicine, Kurume, Japan.

Purpose: To report a case of primary vitreoretinal lymphoma in which a macular hole developed after a diagnostic pars plana vitrectomy.

Methods: A retrospective interventional case report.

Results: A 65-year-old woman presented with worsening vision in the left eye. Fundus examination showed vitreous haze and multifocal, yellow-white infiltrates in the retina and under the retinal pigment epithelium in the left eye. She underwent a diagnostic pars plana vitrectomy in that eye. Undiluted vitreous specimen showed an increased interleukin-10 level (1,470 pg/mL) with an elevated interleukin-10 to interleukin-6 ratio of 15.1; cytologic analysis of the vitreous showed atypical lymphoid cells with large irregular nuclei and scanty cytoplasm. The retinal and sub-retinal pigment epithelial infiltrates responded well to intravitreal methotrexate injections, but a macular hole developed in the left eye. The second pars plana vitrectomy with internal limiting membrane peeling and 20% sulfur hexafluoride gas tamponade successfully closed the macular hole.

Conclusion: Macular hole closure can be accomplished in eyes receiving intravitreal methotrexate injections for treating primary vitreoretinal lymphoma.
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http://dx.doi.org/10.1097/ICB.0000000000000685DOI Listing
April 2021

Pediatric endogenous endophthalmitis with presumed hyposplenism.

Int Med Case Rep J 2017 4;10:7-9. Epub 2017 Jan 4.

Department of Ophthalmology, Kurume University School of Medicine, Kurume, Japan.

Background: Endogenous bacterial endophthalmitis is a rare but potentially devastating intraocular infection that can have severe sight-threatening complications. Most patients with endogenous bacterial endophthalmitis have underlying infectious conditions, such as diabetes or malignancy, which predispose them to infection.

Case Report: A 1-year-old girl presented with cloudiness of the right eye. Ocular examination showed a cloudy cornea in the right eye with conjunctival injection and hypopyon. The intraocular pressure was 43 mmHg, and the fundus could not be visualized. She had an 8-day history of fever, and cerebrospinal fluid analysis showed typical findings of bacterial meningitis. She was clinically diagnosed with bacterial meningitis and endophthalmitis in the right eye and was treated with intravenous, topical, and intravitreal antibiotics and vitrectomy. was isolated from the blood and cerebrospinal fluid cultures, but not from the aqueous and vitreous cultures. Four months later, her pediatrician diagnosed meningitis, but she had no clinical signs of endophthalmitis. Seven years after the initial presentation, the best-corrected visual acuity was 20/40 in the right eye.

Discussion: Endophthalmitis caused by is generally associated with poor visual outcomes; however, the patient in the current case responded well to the treatment. The patient had recurrent bacterial meningitis caused by and within a 4-month period. Magnetic resonance imaging was performed to search for underlying infectious causes and revealed that the patient had an extremely small spleen for her age. Because the spleen is critical for clearing encapsulated bacteria such as or , we speculated that hyposplenism led to the bloodstream infection of and then endogenous endophthalmitis in the right eye.
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http://dx.doi.org/10.2147/IMCRJ.S123524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5221797PMC
January 2017

VITRECTOMY FOR MACULAR RETINOSCHISIS WITHOUT A DETECTABLE OPTIC DISK PIT.

Retina 2017 May;37(5):915-920

Department of Ophthalmology, Kurume University School of Medicine, Fukuoka, Japan.

Purpose: To evaluate the efficacy of vitrectomy in the treatment of macular retinoschisis without a detectable optic disk pit.

Methods: This retrospective interventional case series included eight patients with acquired, unilateral macular retinoschisis with or without foveal detachment. Patients with an optic disk pit, vitreomacular traction, or high myopia were excluded. Six of the eight patients underwent vitrectomy with internal limiting membrane peeling and fluid-air exchange. The surgical outcome was evaluated in terms of the improvement in the macular anatomy and the best-corrected visual acuity.

Results: During vitrectomy, all the six eyes were confirmed to have preexisting posterior vitreous detachment. Macular retinoschisis was resolved or reduced in all the six eyes after vitrectomy. The mean central foveal thickness showed significant improvement at the time of the patient's final visit after vitrectomy. The mean best-corrected visual acuity was 20/52 before surgery and 20/31 at the final visit.

Conclusion: Vitrectomy might be effective for the treatment of macular retinoschisis without an optic disk pit. Although clinically similar to optic pit maculopathy except for the absence of pit, our intraoperative observations of the posterior hyaloid membrane suggest that maculopathy without optic disk pit has a distinct pathogenesis.
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http://dx.doi.org/10.1097/IAE.0000000000001244DOI Listing
May 2017

Regeneration of Vocal Fold Mucosa Using Tissue-Engineered Structures with Oral Mucosal Cells.

PLoS One 2016 5;11(1):e0146151. Epub 2016 Jan 5.

Department of Ophthalmology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.

Objectives: Scarred vocal folds result in irregular vibrations during phonation due to stiffness of the vocal fold mucosa. To date, a completely satisfactory corrective procedure has yet to be achieved. We hypothesize that a potential treatment option for this disease is to replace scarred vocal folds with organotypic mucosa. The purpose of this study is to regenerate vocal fold mucosa using a tissue-engineered structure with autologous oral mucosal cells.

Study Design: Animal experiment using eight beagles (including three controls).

Methods: A 3 mm by 3 mm specimen of canine oral mucosa was surgically excised and divided into epithelial and subepithelial tissues. Epithelial cells and fibroblasts were isolated and cultured separately. The proliferated epithelial cells were co-cultured on oriented collagen gels containing the proliferated fibroblasts for an additional two weeks. The organotypic cultured tissues were transplanted to the mucosa-deficient vocal folds. Two months after transplantation, vocal fold vibrations and morphological characteristics were observed.

Results: A tissue-engineered vocal fold mucosa, consisting of stratified epithelium and lamina propria, was successfully fabricated to closely resemble the normal layered vocal fold mucosa. Laryngeal stroboscopy revealed regular but slightly small mucosal waves at the transplanted site. Immunohistochemically, stratified epithelium expressed cytokeratin, and the distributed cells in the lamina propria expressed vimentin. Elastic Van Gieson staining revealed a decreased number of elastic fibers in the lamina propria of the transplanted site.

Conclusion: The fabricated mucosa with autologous oral mucosal cells successfully restored the vocal fold mucosa. This reconstruction technique could offer substantial clinical advantages for treating intractable diseases such as scarring of the vocal folds.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0146151PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4701435PMC
August 2016

DNA Aptamer Raised against Advanced Glycation End Products Prevents Abnormalities in Electroretinograms of Experimental Diabetic Retinopathy.

Ophthalmic Res 2015 23;54(4):175-80. Epub 2015 Oct 23.

Department of Ophthalmology, Kurume University School of Medicine, Kurume, Japan.

Purpose: Abnormalities in electroretinograms (ERG), such as reduced amplitudes and delayed implicit times of a- and b-wave and oscillatory potentials (OPs), are one of the earliest features of diabetic retinopathy prior to obvious vascular changes in diabetic retinas. We have previously shown that serum levels of advanced glycation end products (AGEs) are correlated with a delayed latency of OPs in type 2 diabetic rats. However, the pathological role of AGEs in ERG abnormalities remains unclear. We examined here whether high-affinity DNA aptamer directed against AGEs (AGE-aptamer) prevents ERG abnormalities in experimental type 1 diabetic retinopathy.

Methods: Streptozotocin-induced diabetic rats or control rats received continuous intraperitoneal infusion of either AGE-aptamer or control aptamer via an osmotic mini pump for 16 weeks. Anthropometric, metabolic, and hemodynamic variables were measured, and an ERG was performed.

Results: Although AGE-aptamer did not affect body weight, fasting and random blood glucose, HbA1c, blood pressure, or lipid parameters, it completely prevented the increase in serum AGE levels as well as the reduction of a- and b-wave and OP amplitudes in diabetic rats.

Conclusion: The present study demonstrated for the first time that AGE-aptamer prevents abnormalities in ERG in experimental diabetic retinopathy probably by blocking the harmful effects of AGEs.
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http://dx.doi.org/10.1159/000440768DOI Listing
June 2016

Risk factors for and circumstances of needlestick and sharps injuries of doctors in operating rooms: A study focusing on surgeries using general anesthesia at Kurume University Hospital, Japan.

J Infect Chemother 2015 Dec 14;21(12):837-41. Epub 2015 Oct 14.

Division of Infection Control and Prevention, Kurume University Hospital, Kurume, Fukuoka 830-0011, Japan; Department of Infection Control and Prevention, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.

Healthcare workers are exposed to serious infectious diseases via needlestick and sharps injuries. The operating room is a particularly important environment in which the risk for needlestick injuries is increased for surgical doctors. According to national surveillance studies, the proportion of needlestick and sharps injuries in operating rooms has been increasing for unknown reasons. In this study, we examined risk factors for and circumstances of injuries in operating rooms by combining and analyzing incidence reports and electronic records of every surgery in Kurume University Hospital (Kurume, Japan). The annual injury rate (reflecting the reporting rate) rose continuously from fiscal years 2007-2012. We conducted analyses focusing on surgeries that used general anesthesia, which accounted for 88.1% of the injuries. An analysis of the time of injury found that the number of injuries increased toward the end of the surgical procedure. A comparative analysis of surgeries by doctors who had experienced injury revealed risk for the injury increased when a procedure ended after 20:00. In addition, a comparative analysis of doctors with and without injury experience who had similar level of operating time per year revealed that the number of working years was not lower in the injured doctors. Although the data analyzed in this study were confined to one university hospital, our approach and these results will form a basis on which to consider more effective measures to prevent injury in operating rooms.
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http://dx.doi.org/10.1016/j.jiac.2015.08.012DOI Listing
December 2015

Evaluation of lid speculum with a drape (LiDrape(®)) for preventing surgical-field contamination.

Clin Ophthalmol 2015 8;9:1227-32. Epub 2015 Jul 8.

Department of Ophthalmology, Kurume University School of Medicine, Kurume, Japan.

Purpose: To compare the degree of surgical-field contamination in cataract surgeries between a new draping method using a lid speculum with a drape (LiDrape(®)) and a conventional draping method.

Methods: Cataract surgery was performed on 21 eyes using LiDrape(®) (LiDrape(®) group) and on 22 eyes using a conventional draping method (conventional group). Contamination was evaluated by bacterial culture of conjunctival sac scrapings and ocular surface irrigation fluid. Conjunctival sac scrapings were collected before and after application of preoperative antibiotics. Ocular surface irrigation fluid was collected before incision placement and during surgery. Bacterial detection rate and types of organisms isolated at these four time points were examined.

Results: Bacterial detection rates were significantly decreased in the LiDrape(®) group at all time points after the application of antibiotics compared with preapplication. Regarding between-group comparisons, the bacterial detection rate in the LiDrape(®) group was only significantly lower than that in the conventional group in the intraoperative sample. Propionibacterium acnes was the most common organism isolated from ocular surface irrigation fluid. The number of P. acnes in the intraoperative sample was significantly lower in the LiDrape(®) group compared with the conventional group. There were no significant differences in detection rates for other bacteria between the groups.

Conclusion: LiDrape(®) was as effective as conventional draping for preventing surgical-field contamination. The number of P. acnes during surgery was significantly lower in the LiDrape(®) group compared with the conventional group, suggesting that LiDrape(®) may contribute to the prevention of postoperative infection.
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http://dx.doi.org/10.2147/OPTH.S81747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4501158PMC
July 2015

First case of fungal keratitis caused by Pestalotiopsis clavispora.

Clin Ophthalmol 2013 27;7:2261-4. Epub 2013 Nov 27.

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

Purpose: To report the isolation of Pestalotiopsis clavispora from the cornea of a patient with recurrent keratitis.

Case Report: A 73-year-old male gardener presented with conjunctival injection and an oval infiltrate with feathery margins in the temporal half of the cornea in the right eye. His ocular history in the right eye included cataract surgery, five episodes of herpes simplex keratitis, three glaucoma surgeries, and bullous keratopathy. He had been treated with corticosteroids for years. Light microscopy of corneal scrapings revealed a filamentous fungus, and fungal keratitis was diagnosed. Treatment with topical voriconazole and pimaricin ointment was commenced. One month later, the infiltrate resolved. The antifungal agents were discontinued 7 months later, and keratitis relapsed 4 days after the discontinuation. The fungus was isolated and identified by molecular techniques as P. clavispora. Based on the results of antifungal susceptibility testing, treatment with topical and intravenous micafungin was initiated. The corneal infiltrate resolved 1 month after the relapse.

Conclusion: Molecular identification of the pathogen, and antifungal susceptibility testing, are useful in treating patients with fungal keratitis caused by a rare human pathogen.
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http://dx.doi.org/10.2147/OPTH.S48732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3848927PMC
December 2013

Beneficial effects of vildagliptin on retinal injury in obese type 2 diabetic rats.

Ophthalmic Res 2013 25;50(4):221-6. Epub 2013 Sep 25.

Department of Ophthalmology, Kurume University School of Medicine, Kurume, Japan.

Background/aims: Vildagliptin is an oral inhibitor of dipeptidyl peptidase-4, an enzyme mainly responsible for inactivating incretins, and one of the widely used drugs for the treatment of type 2 diabetes. However, effects of vildagliptin on retinal injury in diabetes remain unclear. We examined here whether oral administration of vildagliptin inhibited gene expression of inflammatory and thrombogenic parameters in Otsuka Long-Evans Tokushima Fatty rats (OLETF rats), an animal model of obese type 2 diabetes.

Methods: OLETF rats at 22 weeks of age were given vehicle or 3 mg/kg of vildagliptin for another 10 weeks. Gene expression was analyzed in quantitative real-time reverse transcription-polymerase chain reaction.

Results: Vildagliptin significantly inhibited the increase in body weight and decreased average fasting blood glucose in the OLETF rats. Compared with 22-week-old OLETF rats, gene expression levels of vascular endothelial growth factor, intercellular adhesion molecule-1, plasminogen activator inhibitor-1 and pigment epithelium-derived factor were significantly increased in the retinas of OLETF rats at 32 weeks of age, all of which were inhibited by treatment with vildagliptin.

Conclusions: The present study demonstrated for the first time that vildagliptin inhibited inflammatory and thrombogenic reactions in the retinas of obese type 2 diabetic rats. Vildagliptin may play a protective role against diabetic retinopathy.
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http://dx.doi.org/10.1159/000354116DOI Listing
May 2014

Development of a novel disposable lid speculum with a drape.

Clin Ophthalmol 2013 5;7:1575-80. Epub 2013 Aug 5.

Department of Ophthalmology, Kurume University School of Medicine, Kurume, Japan.

Purpose: To evaluate the clinical use of a newly-developed disposable lid speculum with a drape.

Methods: LiDrape® is a cylindrical device that consists of two flexible rings of polyacetal resin with a transparent elastic silicone sheet attached to the rings. The novel device holds the eyelids between the rings, and a hole in the center of the device provides a surgical field. We used the novel device in cataract surgery (75 eyes), glaucoma surgery (eleven eyes), vitrectomy (ten eyes), and intravitreal injection (six eyes) and evaluated its clinical efficacy.

Results: The LiDrape was easy to attach and detach. The novel device was not detached from the eye during surgery. No eyelashes or secretions from the meibomian glands were seen in the surgical field, and the drape provided a sufficient surgical field.

Conclusions: The LiDrape functions as a lid speculum as well as a drape. Our results showed that the novel device is useful for ocular surgeries.
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http://dx.doi.org/10.2147/OPTH.S45132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3741085PMC
August 2013

[Influence of postoperative lens status on intraocular pressure and corneal endothelium following vitrectomy with silicone oil tamponade].

Nippon Ganka Gakkai Zasshi 2013 Feb;117(2):95-101

Department of Ophthalmology, Kurume University School of Medicine, Japan.

Purpose: To evaluate the influence of postoperative lens status on intraocular pressure elevation and corneal endothelial cell loss in patients who underwent pars plana vitrectomy with silicone oil injection for the management of complex retinal detachment.

Patients And Methods: The medical records of 80 eyes of 79 patients who underwent silicone oil removal were reviewed retrospectively. For analysis, eyes were divided by postoperative lens status into 2 groups: pseudophakic eyes (IOL group) and aphakic eyes(aphakic group).

Results: There was a significantly greater decrease in intraocular pressure after silicone oil removal in the aphakic group but not in the IOL group. As compared with the IOL group, the aphakic group showed a significant reduction in endothelial cell density at the time of silicone oil removal.

Conclusion: Patients who underwent silicone oil injection with pseudophakic eyes may have a lower risk of intraocular pressure elevation and corneal endothelial cell loss than those with aphakic eyes.
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February 2013

Rare case of fungal keratitis caused by Plectosporium tabacinum.

Clin Ophthalmol 2012 5;6:1623-7. Epub 2012 Oct 5.

Department of Ophthalmology, Kurume University School of Medicine, Kurume, Fukuoka.

A rare case of fungal keratitis caused by Plectosporium tabacinum is reported. A 78-year-old female gardener presented with conjunctivitis and an oval infiltrate with irregular margins in the nasal half of the cornea in the right eye. Light microscopy of corneal scrapings revealed a filamentous fungus, and a diagnosis of fungal keratitis was made. The patient was admitted into our hospital on February 19, 2008. Treatment with topical miconazole, topical fluconazole, pimaricin ointment, intravenous miconazole, and corneal debridement was commenced. One week later, the infiltrate improved, but the central part of the infiltrate was still deep. Topical fluconazole was switched to topical voriconazole, and intravenous miconazole was switched to intravenous voriconazole. One month after admission, the causative organism was identified by morphology and molecular biological analysis as Plectosporium tabacinum. The corneal infiltrate resolved 3 months after admission. A stromal scar persisted for 3 months after the patient was discharged. This is the first detailed report of fungal keratitis caused by P. tabacinum. Voriconazole was effective in treating this refractory keratitis.
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http://dx.doi.org/10.2147/OPTH.S36318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3468285PMC
October 2012

Vitrectomy for optic disc pit-associated maculopathy with or without preoperative posterior vitreous detachment.

Clin Ophthalmol 2012 23;6:1361-4. Epub 2012 Aug 23.

Department of Ophthalmology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.

Background: The purpose of this study was to evaluate the efficacy of pars plana vitrectomy for the treatment of optic disc pit-associated maculopathy with or without preoperative posterior vitreous detachment.

Methods: We reviewed the clinical records of four consecutive patients who underwent pars plana vitrectomy in one eye for the treatment of optic disc pit-associated maculopathy, with an emphasis on the preoperative condition of the posterior hyaloid membrane.

Results: Two of four eyes were confirmed to have an attached posterior hyaloid membrane, which was subsequently removed during surgery. Following vitrectomy, these two eyes experienced an improvement in visual acuity with complete retinal attachment of the macula. However, the other two eyes, which already had a posterior vitreous detachment at the time of surgery, showed a decrease in visual acuity with persistent maculopathy postoperatively.

Conclusion: Pars plana vitrectomy for optic disc pit-associated maculopathy was beneficial for improving visual acuity in two eyes without preoperative posterior vitreous detachment but not in two eyes with preoperative posterior vitreous detachment. Our study suggests that preoperative assessment of a posterior hyaloid membrane is clinically important in predicting the surgical outcome of optic disc pit-associated maculopathy.
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http://dx.doi.org/10.2147/OPTH.S34962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3430161PMC
October 2012

Clinical experience treating Paecilomyces lilacinus keratitis in four patients.

Clin Ophthalmol 2012 22;6:949-53. Epub 2012 Jun 22.

Department of Ophthalmology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.

Background: Paecilomyces lilacinus is a saprobic fungus that occasionally causes keratitis in infected patients. Voriconazole, a triazole antifungal agent, is often administered to treat P. lilacinus keratitis, because it is resistant to many antifungal agents. However, some patients may not require voriconazole. Here, we report our experience of treating this infection and compare outcomes between patients treated with or without voriconazole.

Subjects: We retrospectively reviewed four cases of infectious keratitis caused by P. lilacinus and compared treatment course and outcomes among the four cases.

Observations: P. lilacinus was isolated from corneal cultures in all four cases. Three cases developed corneal perforation and underwent keratoplasty. Voriconazole was given in two cases with severe and refractory infection. Both required long-term treatment despite the effectiveness of voriconazole. They also had a medical history of diabetes and corticosteroid therapy. In two cases that were not treated with voriconazole, the eye conditions improved with a short treatment period (2-3 weeks). Neither of these cases had a medical history of diabetes, nor had they used corticosteroids.

Conclusion: Although voriconazole is the most useful antifungal agent for treating P. lilacinus keratitis, this infection can be resolved by other treatments. Voriconazole should be offered to patients with diabetes and/or prior corticosteroid use.
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http://dx.doi.org/10.2147/OPTH.S29379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392915PMC
October 2012

Characteristics and surgical outcomes of pediatric rhegmatogenous retinal detachment.

Clin Ophthalmol 2012 20;6:939-43. Epub 2012 Jun 20.

Department of Ophthalmology, Kurume University School of Medicine, Kurume, Japan.

Purpose: To describe the characteristics and surgical outcomes of pediatric rhegmatogenous retinal detachment.

Methods: A retrospective study of pediatric patients (15 years old or younger) who had undergone primary surgery for rhegmatogenous retinal detachment was conducted. Patients were divided into five groups according to the predisposing factors: trauma (group 1), myopia (group 2), atopic dermatitis (group 3), congenital or developmental anomalies (group 4), and others (group 5).

Results: A total of 48 eyes of 44 patients were included in this study. There were 18 eyes (37.5%) in group 1, twelve eyes (25.0%) in group 2, six eyes (12.5%) in group 3, five eyes (10.4%) in group 4, and seven eyes (14.6%) in group 5. The initial retinal reattachment rate was 89% in group 1, 100% in group 2, 83% in group 3, 20% in group 4, and 86% in group 5 (P = 0.002). The final retinal reattachment rate was 100% in group 1, 100% in group 2, 100% in group 3, 80% in group 4, and 86% in group 5 (P = 0.16). The frequency of visual acuity of 0.1 or better after surgery was 100% in group 1, 92% in group 2, 83% in group 3, 40% in group 4, and 71% in group 5 (P = 0.01).

Conclusion: The overall surgical outcome was successful, but the patients in group 4 had the lowest initial reattachment rate and the worst visual prognosis.
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http://dx.doi.org/10.2147/OPTH.S31765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392924PMC
October 2012

A clinically challenging diagnosis of adenoma of the retinal pigment epithelium presenting with clinical features of choroidal hemangioma.

Clin Ophthalmol 2012 26;6:497-502. Epub 2012 Mar 26.

Department of Ophthalmology, Kurume University School of Medicine, Kurume.

Background: Adenoma of the retinal pigment epithelium (RPE) is a rare intraocular tumor that can simulate other pigmented tumors such as choroidal melanoma. We report a case of non-pigmented adenoma of the RPE initially diagnosed as choroidal hemangioma.

Case Report: A 42-year-old woman presented to Kurume University Hospital in November 1992 with an orange-yellow tumor nasal to the optic disc in the left fundus. The tumor was 9.0 × 9.0 mm in diameter, 6.0 mm thick, and was characterized by high intensity on T1-weighted magnetic resonance imaging (MRI), low intensity on T2-weighted MRI, and enhancement on gadolinium MRI. Fluorescein angiography revealed early hypofluorescence and late hyperfluorescence of the tumor and retinal feeder vessels. By April 1996, exudate had developed around the tumor margins. The patient was treated with external beam radiation therapy (20 Gy) in July 1996, but the tumor did not diminish in size. Subsequently, she developed extensive loss of vision due to total retinal detachment. Accordingly, her left eye was enucleated in June 2005 because of severe ocular pain due to absolute glaucoma. Histopathological examination indicated that the tumor was contiguous with the normal surrounding RPE and was composed of cords and tubules of mostly non-pigmented spindle-shaped cells with round to oval nuclei and a small amount of cytoplasm containing melanin granules. The tumor cells were immunoreactive for vimentin, S-100 protein, and cytokeratin 18. The final diagnosis was adenoma of the RPE.

Conclusion: Adenoma of the retinal pigment epithelium may be associated with incompetent vessels leading to serous retinal detachment and extensive visual loss, and may exhibit clinical characteristics similar to choroidal hemangioma.
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http://dx.doi.org/10.2147/OPTH.S28933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3334219PMC
October 2012

Spectral-domain optical coherence tomography of the choroid in choroidal osteoma.

Ophthalmic Surg Lasers Imaging 2011 Dec 8;42 Online:e118-21. Epub 2011 Dec 8.

Department of Ophthalmology, Kurume University School of Medicine, Kurume, Japan.

The authors report spectral-domain optical coherence tomography (SD-OCT) findings in a patient with decalcifying choroidal osteoma accompanied by a choroidal neovascular membrane and serous retinal detachment. A 13-year-old girl was found to have a choroidal osteoma in the left eye. The clinical diagnosis was confirmed by B-scan ultrasonography, computed tomography, and fluorescein and indocyanine green angiography. The SD-OCT findings over the decalcified portion included serous retinal detachment, photoreceptor outer segment disorganization, retinal pigment epithelial atrophy, deformed Bruch's membrane, and choroidal neovascular membrane. In contrast, the retinal structures over the calcified portion appeared to be preserved. SD-OCT showed loss of a vascular appearance and increased thickness in the affected choroid, especially in the decalcified portion. Choroidal thickening may be associated not only with choroidal osteomas, but also with tumor decalcification. These unique features on SD-OCT may be important in understanding poor visual prognosis when decalcification involves the fovea.
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http://dx.doi.org/10.3928/15428877-20111201-04DOI Listing
December 2011

Recurrence after spontaneous resolution of an idiopathic epiretinal membrane.

Case Rep Ophthalmol 2011 Jan 5;2(1):55-8. Epub 2011 Feb 5.

Departments of Ophthalmology, Kurume University School of Medicine, Kurume, Japan.

We report a case of recurrent epiretinal membrane (ERM) after spontaneous resolution of an idiopathic ERM. A 65-year-old female demonstrated a spontaneous improvement in visual acuity from 0.1 to 1.2 in her left eye attributable to spontaneous resolution of idiopathic ERM due to posterior vitreous detachment. Thereafter, however, her visual acuity again decreased to 0.2 because of the recurrence of ERM. Her visual acuity improved to 0.8 after surgical removal. A microscopic examination of the excised specimen showed a characteristic undulating internal limiting membrane (ILM) and a continuous sheet of cells overlying the inner surface of the ILM. This case report illustrates that although spontaneous ERM resolution is rare, there is a possibility of recurrence even after spontaneous ERM resolution.
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http://dx.doi.org/10.1159/000324462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3219446PMC
January 2011

Retinal nerve fiber layer thickness changes following optic neuritis caused by multiple sclerosis.

Jpn J Ophthalmol 2011 Jan 18;55(1):45-8. Epub 2011 Feb 18.

Department of Ophthalmology, Kurume University School of Medicine, Kurume, Japan.

Purpose: To evaluate the peripapillary retinal nerve fiber layer (RNFL) thickness with scanning laser polarimetry in patients with optic neuritis (ON) caused by multiple sclerosis.

Methods: Peripapillary RNFL thickness was measured with a GDx VCC in 14 eyes of 13 patients with ON (nonrecurrent group), in 18 eyes of 11 patients with recurrent ON (recurrent group), and in 48 eyes of 48 healthy subjects (healthy group). The temporal, superior, nasal, inferior thickness (TSNIT) average, superior average, and inferior average of GDx VCC measurements were compared across the three groups. We calculated correlation coefficients between each of the three GDx VCC parameters and both the mean deviation (MD) of the Humphrey 30-2 full threshold visual field and the visual acuity (VA).

Results: The three parameters showed statistically significant differences across the three groups. There was no correlation between any of the three GDx VCC parameters and MD or VA in the nonrecurrent group, but there was significant correlation between each of the three GDx VCC parameters and MD in the recurrent group.

Conclusions: ON caused morphological changes in the peripapillary RNFL, and recurrent ON aggravated the deterioration and caused diffuse rather than regional damage to the peripapillary RNFL.
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http://dx.doi.org/10.1007/s10384-010-0902-1DOI Listing
January 2011

Pigment epithelium-derived factor (PEDF) inhibits proximal tubular cell injury in early diabetic nephropathy by suppressing advanced glycation end products (AGEs)-receptor (RAGE) axis.

Pharmacol Res 2011 Mar 27;63(3):241-8. Epub 2010 Nov 27.

Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan.

Pigment epithelium-derived factor (PEDF) is a multifunctional glycoprotein with anti-angiogenic and anti-inflammatory properties, and it could block the development and progression of experimental diabetic retinopathy. However, a role for PEDF in early experimental diabetic nephropathy is not fully understood. Advanced glycation end products (AGEs) and their receptor (RAGE) axis stimulates oxidative stress generation and subsequently evokes inflammatory and fibrogenic reactions in renal tubular cells, thereby playing a role in diabetic nephropathy. Therefore, this study investigated whether PEDF could prevent AGE-elicited tubular cell injury in early diabetic nephropathy. Human proximal tubular cells were incubated with or without AGE-bovine serum albumin in the presence or absence of PEDF. Streptozotocin-induced diabetic rats were treated with or without intravenous injection of PEDF for 4 weeks. Gene expression was analyzed by quantitative real-time reverse transcription-polymerase chain reactions. Reactive oxygen species (ROS) was measured with dihydroethidium staining. PEDF or antibodies raised against RAGE inhibited the AGE-induced RAGE gene expression and subsequently reduced ROS generation, monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor-β (TGF-β), fibronectin and type IV collagen mRNA levels in proximal tubular cells. RAGE gene expression, ROS generation and MCP-1 and TGF-β mRNA levels were significantly increased in diabetic kidney, which were suppressed by administration of PEDF. Our present data suggest that PEDF could play a protective role against tubular injury in diabetic nephropathy by attenuating the deleterious effects of AGEs via down-regulation of RAGE expression. Administration of PEDF may offer a promising strategy for halting the development of diabetic nephropathy.
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http://dx.doi.org/10.1016/j.phrs.2010.11.008DOI Listing
March 2011

Protective role of pigment epithelium-derived factor (PEDF) in early phase of experimental diabetic retinopathy.

Diabetes Metab Res Rev 2009 Oct;25(7):678-86

Department of Ophthalmology, Kurume University School of Medicine, Kurume, Japan.

Background: Pigment epithelium-derived factor (PEDF) is the most potent inhibitor of angiogenesis in the mammalian eye, thus suggesting that PEDF may protect against proliferative diabetic retinopathy. However, a role for PEDF in early diabetic retinopathy remains to be elucidated. We investigated here whether and how PEDF could prevent the development of diabetic retinopathy.

Methods: Streptozotocin-induced diabetic rats were treated with or without intravenous injection of PEDF for 4 weeks. Early neuronal derangements were evaluated by electroretinogram (ERG) and immunofluorescent staining of glial fibrillary acidic protein (GFAP). Expression of PEDF and 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative stress, was localized by immunofluorescence. Vascular endothelial growth factor (VEGF) and p22phox expression were evaluated with western blots. Breakdown of blood retinal barrier (BRB) was quantified with fluorescein isothiocynate (FITC)-conjugated dextran. NADPH oxidase activity was measured with lucigenin luminescence.

Results: Retinal PEDF levels were reduced, and amplitudes of a- and b-wave in the ERG were decreased in diabetic rats, which were in parallel with GFAP overexpression in the Müller cells. Further, retinal 8-OHdG, p22phox and VEGF levels and NADPH oxidase activity were increased, and BRB was broken in diabetic rats. Administration of PEDF ameliorated all of the characteristic changes in early diabetic retinopathy.

Conclusions: Results suggest that PEDF could prevent neuronal derangements and vascular hyperpermeability in early diabetic retinopathy via inhibition of NADPH oxidase-driven oxidative stress generation. Substitution of PEDF may offer a promising strategy for halting the development of diabetic retinopathy.
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http://dx.doi.org/10.1002/dmrr.1007DOI Listing
October 2009

Genetics of Behçet disease inside and outside the MHC.

Ann Rheum Dis 2010 Apr 13;69(4):747-54. Epub 2009 Aug 13.

Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Yokohama, Kanagawa, Japan.

Background: Behçet disease (BD) is a rare, chronic, systemic, inflammatory disorder characterised by recurrent ocular, genital and skin lesions. Although its aetiology is still uncertain, an intricate interplay between the environment (eg, viruses) and the host seems to initiate and/or perpetuate the disease, although the mechanism remains speculative. Since the identification of HLA-B*5101 (and more recently of MICA) as a susceptibility locus for BD, the identification of additional genetic locus/loci, whether inside, or perhaps more importantly outside the MHC has clearly stalled.

Objective: To carry out a genome-wide association study (GWAS) of BD.

Methods: 300 Japanese patients with BD and an equal number of controls were recruited. The samples were screened using a dense panel of 23 465 microsatellites (MS) covering the entire genome.

Results: The six best (of a total of 147) positively associated MS with BD were identified. Of these six, two were located within the human leucocyte antigen (HLA) class I region itself. Although one of these was clearly reminiscent of the association with HLA-B, the second, not in linkage disequilibrium with the former, was in the telomeric side of the class I region and remained to be formally identified. HLA genotyping and haplotype analysis conclusively led to the deciphering of a dual, independent, contribution of two HLA alleles to the pathogenesis of BD: HLA-B*5101 and HLA-A*26.

Conclusions: This GWAS highlights the premier genetic susceptibility locus for BD as the major histocompatibility complex itself, wherein reside two independent loci: HLA-B and HLA-A.
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http://dx.doi.org/10.1136/ard.2009.108571DOI Listing
April 2010

Seprafilm as a new antifibrotic agent following trabeculectomy in rabbit eyes.

Jpn J Ophthalmol 2009 Mar 31;53(2):164-170. Epub 2009 Mar 31.

Department of Ophthalmology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.

Purpose: To investigate the efficacy of Seprafilm (Genzyme, Framingham, MA, USA) in preventing postoperative adhesion between the conjunctiva and sclera after glaucoma filtering surgery.

Methods: A subconjunctival pocket was created and Seprafilm was inserted into the pocket in nine rabbits (Seprafilm group), whereas in a second group, a subconjunctival pocket was created in nine rabbits but no Seprafilm was inserted (non-Seprafilm group). The postoperative adhesion force was measured 4 weeks after surgery. For the trabeculectomy study, trabeculectomy was performed and Seprafilm placed on the scleral flap in five rabbits (Seprafilm trabeculectomy group), whereas in a second group, trabeculectomy was performed in five rabbits but no Seprafilm was placed (non-Seprafilm trabeculectomy group). Filtering bleb formation and intraocular pressure (IOP) was evaluated on days 1, 3, 5, 7, 14, 21, and 28 following surgery. The eyes were enucleated for histologic evaluation 4 weeks after surgery.

Results: The mean adhesive force between the conjunctiva and sclera in the Seprafilm group (125.6 +/- 94.5 mmHg) was lower than that of the non-Seprafilm group (263.3 +/- 79.3 mmHg) (P = 0.0041, unpaired t test). A more prominent bleb was observed in the Seprafilm trabeculectomy group than in the non-Seprafilm trabeculectomy group. Histologically, the subconjunctival space was larger in the Seprafilm trabeculectomy group than in the non-Seprafilm trabeculectomy group. Mean IOP was significantly lower in the Seprafilm trabeculectomy group (9.9 +/- 0.6 mmHg) than in the non-Seprafilm trabeculectomy group (11.9 +/- 0.7 mmHg) 4 weeks after surgery (P = 0.0044, unpaired t test).

Conclusions: Seprafilm can reduce postoperative conjunctiva-sclera adhesion and may be a desirable antifibrotic agent for trabeculectomy in the early stages of wound repair.
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http://dx.doi.org/10.1007/s10384-008-0638-3DOI Listing
March 2009

Positive correlation of pigment epithelium-derived factor and total antioxidant capacity in aqueous humour of patients with uveitis and proliferative diabetic retinopathy.

Br J Ophthalmol 2007 Sep 27;91(9):1133-4. Epub 2007 Mar 27.

Department of Ophthalmology, Kurume University School of Medicine, Kurume, Japan.

Background/aims: There are several animal studies to suggest that pigment epithelium-derived factor (PEDF) may exert beneficial effects on diabetic retinopathy and uveitis by acting as an endogenous antioxidant. However, the interrelationship between PEDF and total antioxidant capacity in the human eye remains to be elucidated. In this study, PEDF and total antioxidant levels were determined in the aqueous humour of patients with proliferative diabetic retinopathy (PDR) and uveitis, and the relationship between these two markers was investigated.

Methods: Aqueous humour levels of PEDF and total antioxidant capacity were determined by an ELISA system in 34 uveitis and 9 PDR samples.

Results: Aqueous humour levels of PEDF and total antioxidant capacity were significantly lower in patients with PDR than those with uveitis (1.8+/-0.2 microg/ml vs 6.4+/-0.8 microg/ml and 0.17+/-0.03 mmol/l vs 0.85+/-0.05 mmol/l, respectively, p<0.01). A positive correlation between PEDF and total antioxidant capacity was found in patients with PDR and uveitis (r = 0.33, p<0.05).

Conclusion: This study demonstrated that PEDF levels were associated with total antioxidant capacity in aqueous humour levels in humans. These observations suggest that substitution of PEDF may be a therapeutic target for oxidative stress-involved eye diseases, especially PDR.
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http://dx.doi.org/10.1136/bjo.2007.115188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1954896PMC
September 2007

Positive correlation between pigment epithelium-derived factor and monocyte chemoattractant protein-1 levels in the aqueous humour of patients with uveitis.

Br J Ophthalmol 2007 Jun 13;91(6):737-8. Epub 2006 Dec 13.

Department of Medicine, Division of Cardiovascular Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan.

Aim: To evaluate whether aqueous humour levels of pigment epithelium-derived factor (PEDF) are associated with monocyte chemoattractant protein-1 (MCP-1) in patients with uveitis.

Methods: Aqueous humour levels of MCP-1 and PEDF were determined by ELISA in 34 uveitis samples and 9 cataract control samples.

Results: Aqueous humour MCP-1 and PEDF levels were significantly higher in patients with infectious or non-infectious uveitis than in controls (mean (SD) 32.3 (10.7) ng/ml vs 4.48 (1.10) ng/ml vs 0.47 (0.10) ng/ml, and 8.40 (1.30) microg/ml vs 5.01 (0.92) microg/ml vs 1.32 (0.22) microg/ml, respectively, p<0.001). A positive correlation between PEDF and MCP-1 was found in patients with uveitis (r = 0.39, p<0.01).

Conclusion: The results demonstrated that aqueous humour levels of PEDF were positively associated with MCP-1 in patients with uveitis. The present observations suggest that aqueous humour levels of PEDF may be a marker of inflammation in uveitis.
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http://dx.doi.org/10.1136/bjo.2006.109843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1955592PMC
June 2007

Increased levels of pigment epithelium-derived factor in aqueous humor of patients with uveitis.

Br J Ophthalmol 2007 Feb 14;91(2):149-50. Epub 2006 Sep 14.

Department of Ophthalmology, Kurume University School of Medicine, Kurume 830-0011, Japan.

Aim: To evaluate whether aqueous humor levels of pigment epithelium-derived factor (PEDF) are increased in patients with uveitis

Methods: Aqueous humor levels of PEDF and tumour necrosis factor alpha (TNFalpha) were determined by ELISA in 34 uveitis samples and 9 cataract control samples.

Results: Aqueous humor PEDF and TNFalpha levels were significantly higher in patients with uveitis than in controls (mean (SD) 6.4 (0.8) v 1.3 (0.2) microg/ml and 14.7 (3.8) v 4.2 (0.4) pg/ml, respectively; p<0.01). A positive correlation between PEDF and TNFalpha was found in patients with uveitis (r = 0.40, p<0.01). Furthermore, PEDF levels in aqueous humor were increased in proportion to the disease activity of uveitis.

Conclusion: The results show that aqueous humor levels of PEDF are increased in patients with uveitis. Our observations suggest that aqueous humor levels of PEDF may be increased as a countersystem against inflammation in uveitis.
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http://dx.doi.org/10.1136/bjo.2006.103804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1857622PMC
February 2007
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