The Change in Neutrophil Lymphocyte Ratio from the First to the Last Repeat Prostate Biopsy Proposed as a Marker of Carcinogenesis.

INTRODUCTION: We investigated whether the change in the neutrophil lymphocyte ratio (NLR) from the first to the last repeat prostate biopsy (ΔNLR) could be the diagnostic tool or not for prostate cancer (PCa) detection. MATERIALS AND METHODS: We retrospectively evaluated medical records of men who had undergone repeat prostate biopsy. The investigated parameters were white blood cell, neutrophil, lymphocyte counts, NLR at the last prostate biopsy, ΔNLR, prostate-specific antigen (PSA), PSA density (PSAD), and PSA velocity. Exclusion criteria were the presence of cancers other than prostate origin, medication, and diseases which induce the change of NLR. RESULTS: A total of 301 men who had undergone repeat prostate biopsy were selected for this study. After applying exclusion criteria, 223 patients were included. Of these patients, 94 were diagnosed with PCa (Group I) and 129 with no malignancy (Group II). Only a single patient had metastasis. On evaluating the area under the receiver operating characteristic curve of all study parameters, ΔNLR was the most accurate marker, followed by PSAD and then NLR measured at the last biopsy. CONCLUSIONS: ΔNLR was the most accurate marker to improve the total predictive value in repeat prostate biopsy for diagnosing PCa.

Comparisons of focal macular electroretinograms after indocyanine green-, brilliant blue G-, or triamcinolone acetonide-assisted macular hole surgery.

PURPOSE: To compare the effects of indocyanine green (ICG)-, brilliant blue G (BBG)-, or triamcinolone acetonide (TA)-assisted internal limiting membrane (ILM) peeling during macular hole (MH) surgery on the different components of the focal macular electroretinograms (fmERGs). METHODS: Forty-eight eyes of 48 patients with a macular hole were randomly divided into those undergoing ICG-, BBG-, or TA-assisted vitrectomy (n = 16 for each group). All patients had combined cataract and macular hole surgery with ILM peeling. The fmERGs were recorded before, and 1, 3, 6, 9, and 12 months postoperatively. The amplitudes and implicit times of the a- and b-waves, the amplitudes of the sum of the oscillatory potentials (ΣOPs), and the photopic negative responses (PhNRs) were analyzed. RESULTS: The amplitudes of all of the components of the fmERGs gradually increased with time after surgery (P < 0.005). The implicit times of the a- and b-waves were significantly prolonged at 1 month (P < 0.01) and then gradually returned to the baseline times. No significant differences were found in these changes among the groups. In pooled data from the 48 patients, the PhNR amplitude increased more than the a- and b-waves and the ΣOPs amplitudes at every time point after 3 months (P < 0.005). CONCLUSIONS: The lack of significant differences on the different components of the fmERGs indicates that none of the three agents was toxic to the macula. After closure of a MH, the function of the retinal ganglion cells may recover more than that of the other neural elements in the macular area.

Axitinib-induced proteinuria and efficacy in patients with metastatic renal cell carcinoma.

BACKGROUND: No report has evaluated axitinib-induced proteinuria as a biomarker for predicting treatment efficacy and survival of patients with metastatic renal cell carcinoma (mRCC). METHODS: The subjects were patients with mRCC treated with axitinib at Kinki University Hospital from February 2008 to November 2014. Clinical records were retrospectively reviewed including baseline patient characteristics, time-dependent changes of urinary protein status, computed tomography scans of metastatic lesions, treatment duration with axitinib, and survival time. RESULTS: A total of 45 patients were evaluable. Median tumor shrinkage rates were 32.3 and 35.0 % in patients with urinary protein increases ≥+2 and <+2, respectively (p = 0.496). Objective response rates were also similar between the two groups. Median progression-free survival (PFS) times with axitinib were 13.5 months [95 % confidence interval (CI) 0.0-27.5] and 11.0 months (95 % CI 0.0-26.7) in patients with urinary protein increases ≥+2 and <+2, respectively (p = 0.975). The maximum tumor shrinkage rate with axitinib was significantly associated with PFS with axitinib as a result of multivariate analysis (p = 0.002). Median overall survival (OS) times were 39.8 months (95 % CI 12.7-67.0) and 25.4 months (95 % CI 11.2-39.6) in patients with axitinib-induced urinary protein increases ≥+2 and <+2, respectively (p = 0.250). The number of metastatic sites (p = 0.006), the MSKCC risk (p = 0.009), and the maximum tumor shrinkage rate with axitinib (p = 0.019) were significantly associated with OS as a result of multivariate analysis. CONCLUSIONS: The degree of urinary protein increase during axitinib treatment was not associated with objective response, PFS, and OS in mRCC patients treated with axitinib.

Differences in adverse event profiles between everolimus and temsirolimus and the risk factors for non-infectious pneumonitis in advanced renal cell carcinoma.

BACKGROUND: There have been few reports of the differences in safety between the mammalian target of rapamycin inhibitors, everolimus and temsirolimus. The purpose of this study is to compare the adverse event profiles of both agents and to estimate the risk factors for non-infectious pneumonitis in patients with advanced renal cell carcinoma on the basis of our real-world clinical experience. METHODS: Data from 218 consecutive patients that received either everolimus or temsirolimus for advanced renal cell carcinoma at five Japanese centers were retrospectively analyzed. Chi-squared test and univariate and multivariate logistic regression analyses were performed to investigate the differences in adverse event profiles and the risk factors associated with non-infectious pneumonitis, respectively. RESULTS: A total of 196 patients were evaluable. In the everolimus group compared with temsirolimus, stomatitis (56 vs 30 %, p < 0.001) and non-infectious pneumonitis (38 vs 22 %, p = 0.018) were more frequently observed, and asthenia (11 vs 23 %, p = 0.027), rash (20 vs 36 %, p = 0.018), and fatigue (33 vs 48 %, p = 0.032) occurred less frequently in all grades. On multivariate analysis, male gender (odds ratio 3.65; 95 % confidence interval 1.44-9.26, p = 0.007) and everolimus treatment (odds ratio 2.00; 95 % confidence interval 1.01-3.96, p = 0.046) were significantly associated with development of non-infectious pneumonitis. CONCLUSION: Our findings suggest that adverse event profiles may differ between everolimus and temsirolimus and that non-infectious pneumonitis may occur more frequently in patients treated with everolimus than temsirolimus. Further investigations are needed to confirm these results.

Prospective evaluation of the safety of transrectal ultrasound-guided transperineal prostate biopsy based on adverse events.

BACKGROUND: Although transperineal (TP) prostate biopsy is growing in popularity, its safety has not been evaluated based on extensive studies. We prospectively assessed the adverse events associated with transrectal ultrasound (TRUS)-guided TP 16-core prostate biopsy at a single institution. PATIENTS AND METHODS: We enrolled 2,086 males who underwent first-time TRUS-guided TP prostate biopsy under lumbar spinal anesthesia at Chiba Cancer Center between 2009 and 2013. Eight adverse events were assessed prospectively using a purpose-designed questionnaire. The prevalence and duration of all adverse events were evaluated. We performed subgroup analyses for hematuria and urinary retention in relation to clinical factors. RESULTS: Questionnaires were collected from 1,663 cases (79.7 %). The cancer detection rate was 53.5 % in all patients. The prevalence and duration of complications were as follows: hematuria, 73.4 % and 4.51 ± 2.88 days; perineal bleeding, 7.1 % and 2.20 ± 2.24 days; hematospermia 14.4 %; dysuria, 15.7 % and 3.12 ± 2.71 days; urinary tract pain, 49.5 % and 2.43 ± 2.08 days; perineal pain, 35.5 % and 3.53 ± 2.59 days; fever ≥37 °C, 1.7 % and 1.79 ± 1.72 days; and headache, 22.1 % and 3.40 ± 2.10 days. Seventeen patients (1.1 %) required indwelling urethral catheterization for grade 2 urinary retention. Pre-biopsy International Prostate Symptom Score (p = 0.014) was an independent related factor for hematuria. Prostate volume (p = 0.001) was an independent related factor for grade 2 urinary retention. CONCLUSIONS: TRUS-guided TP prostate biopsy under lumbar spinal anesthesia can be performed safely with only minor adverse events.

Comparisons of cone electroretinograms after indocyanine green-, brilliant blue G-, or triamcinolone acetonide-assisted macular hole surgery.

PURPOSE: To compare the function of retinal ganglion cells (RGCs) using the photopic negative response (PhNR) in patients who had undergone indocyaine green (ICG)-assisted, brilliant blue G (BBG)-assisted, or triamcinolone acetonide (TA)-assisted internal limiting membrane (ILM) peeling during macular hole (MH) surgery. METHODS: Forty-eight eyes of 48 patients with a macular hole were randomly divided into those undergoing ICG-assisted, BBG-assisted, or TA-assisted vitrectomy (n = 16 for each group). Full-field cone ERGs were recorded before and 1, 3, 6, 9, and 12 months postoperatively. The amplitudes and implicit times of the a-waves and b-waves and the amplitudes of the oscillatory potentials (OPs) and PhNRs were measured. The mean deviations (MDs) of standard automated perimetry and the best-corrected visual acuity (BCVA) were measured. The circumferential retinal nerve fiber layer (RNFL) thickness was evaluated by SD-OCT. RESULTS: All macular holes were closed with a significant improvement of the BCVA and MD without differences among the groups. There was no significant difference between the preoperative and postoperative RNFL thickness. The implicit times of the a-waves and b-waves were significantly prolonged, and the ΣOPs amplitude was significantly decreased postoperatively in all groups. These ERG changes were not significantly different among the groups. The postoperative PhNR amplitudes were significantly lower in the ICG group than in the BBG or TA group. CONCLUSIONS: The results indicate that the PhNR may detect subclinical impairments of RGCs caused by the possible toxic effect of ICG. This finding adds to the data that BBG and TA may be safer than ICG for use during MH surgery.

Efficacy of traditional and alternative sunitinib treatment schedules in Japanese patients with metastatic renal cell carcinoma.

We report the adverse events and efficacy of traditional (4 weeks on 2 weeks off) and alternative sunitinib treatment schedules for Japanese patients with metastatic renal cell carcinoma. We retrospectively investigated 54 patients who received sunitinib for metastatic renal cell carcinoma between May 2006 and June 2012: 32 received a traditional treatment schedule and 22 received an alternative schedule. According to the Memorial Sloan-Kettering Cancer Center risk classification, five patients had favorable prognoses, 42 had intermediate prognoses and seven had poor prognoses. The mean observation periods were 16.3 and 20 months for the traditional and alternative schedule groups, respectively. Adverse events were significantly less common in the alternative schedule group, including most high-grade events. In the traditional and alternative schedule groups, median times to failure were 4.1 and 11.6 months (P = 0.040), median progression-free survival times were 4.1 and 11.3 months (P = 0.031), and median overall survival times were 12.0 and 32.1 months (P = 0.018), respectively. Each of these measures was better in the group of patients who received an alternative treatment schedule, suggesting that individualized changes to the sunitinib administration schedule can be effective.

[Ophthalmic relief activities conducted by Iwate Medical University after the Great East Japan Earthquake].

PURPOSE: To report the ophthalmic relief activities conducted by Iwate Medical University after the Great East Japan Earthquake of March 11, 2011. SUBJECTS AND METHODS: A retrospective review was conducted of the medical records of patients who visited emergency ophthalmic clinics opened at Yamada-cho, Otsuchi-cho and Rikuzentakada-shi from March 30, 2011 to June 30, 2011. RESULTS: We provided ophthalmic medical care for 14 days at Yamada-cho and Otsuchi-cho, and for 9 days at Rikuzentakada-shi. During this period, 1371 new patients (total of 2015 patients) visited the clinics. The main motives were a desire for prescription of medication, treatment of ocular symptoms and correction of refractive error and presbyopia. The major diseases were cataract, pseudophakia, refractive error, presbyopia and conjunctivitis. Only a few patients had a foreign body in the eye or ocular trauma. Among the 207 patients with contact lenses, 24 patients were wearing them beyond their replacement date, and contact lens care was insufficient in 35 patients. Among 179 patients with glaucoma who were checked for intraocular pressure, 61 patients had an IOP greater than 21 mmHg. CONCLUSIONS: Although many patients sought eye drops for chronic eye diseases and correction of refractive error and presbyopia, patients with ocular injuries were few. It is important to prepare for whatever needs patients in emergency circumstances may present.

Giant adrenal pseudocyst removed using robot-assisted surgery.

Introduction: Adrenal cysts are relatively rare and often asymptomatic. Surgical treatment is indicated for symptomatic cases with cysts >6 cm, suspected bleeding, and those that cannot be distinguished from malignant illness based on imaging findings. There have often been cases of giant cysts that were difficult to treat using laparoscopic surgery. Case presentation: A 39-year-old woman presented with fever and upper abdominal pain. Abdominal computed tomography and magnetic resonance imaging revealed a 95 × 80-mm left adrenal cyst. As malignant disease could not be ruled out, and the patient was symptomatic, we opted for robot-assisted left adrenalectomy. The pathological findings indicated an adrenal pseudocyst. Conclusions: This is the second report of the successful robot-assisted removal of a giant adrenal cyst.

[A patient with an ectopic ureteral opening diagnosed on the basis of pus discharge from the perineal region].

The patient was a 53-year-old woman with chief complaints of repeated pyrexia and pus discharge from the perineal region. A macroscopic examination revealed the presence of a fistula in the anterior wall of the vagina ; magnetic resonance imaging, retrograde urography through the fistula, and excretory urography indicated that the fistula was a complete left ureteral duplication with an opening on the anterior wall of the vagina. Laparoscopic ureterectomy of the left ectopic ureter was performed to achieve a complete cure. The ectopic ureteral opening led to a blind canal in the superior pole of the kidney. No postoperative complications were observed, and the symptoms disappeared. This is a rare case in which the patient, who did not have any symptoms until she became an adult, was diagnosed as having left ureteral duplication with the opening on the anterior wall of the vagina when pus was drained from the perineal region.

[Analysis of prognostic factor in 52 castration-resistant prostate cancer treated with docetaxel].

The prognostic factor was retrospectively analyzed in 52 castration-resistant prostate cancer treated with docetaxel (DTX) in our institutions from April, 2006 to August, 2009. The treatment outcomes were decided with prostate specific antigen (PSA) progression-free survival and overall survival. These were calculated by Kaplan-Meier methods and tested with Log-rank test. Median PSA progression-free survival was 8.8 months and median overall survival was 24.1 months. Prognostic factors on PSA progression were PSA value before DTX treatment and rate of PSA decrement after DTX treatment. Prognostic factors on overall survival were Gleason score (GS), PSA value before DTX treatment, rate of PSA decrement after DTX treatment and positive of bone metastasis in Log-rank test. Odds ratio of PSA ≧20 ng/ml before DTX treatment was 2.99 and PSA decreasing rate < 30% was 3.65. These were statistically significant (p < 0.001) risk factors in the overall survival.

[Intensity-modulated radiation therapy (IMRT) for localized and locally advanced prostate cancer: initial result and morbidity].

OBJECTIVE: We report the short-term results of intensity modulated radiotherapy (IMRT) for localized and locally advanced prostate cancer. PATIENTS AND METHODS: The study was conducted on the total of 53 patients receiving IMRT in our hospital from July 2007 to November 2010 (25 patients receiving IMRT alone and 28 patients receiving neoadjuvant hormone therapy before IMRT). RESULTS: The period of neoadjuvant hormone therapy was 1 to 29 months (median 7 months). 6 patients were in the low risk group, 15 in the intermediate risk group, and 32 in the high risk group according to the D'Amico risk classification criteria. With the prescribed dose of 70 Gy to 74 Gy, prostates were irradiated locally. The follow-up period was 18 to 48 months (median 30 months). The overall 3-year PSA relapse-free survival rate was 90.0%. The 3-year PSA relapse-free survival rate for the patients in low-, intermediate- and high-risk groups were 80.0%, 93.3% and 90.0%, respectively. The 3-year PSA relapse-free survival rate based on the presence or absence of neoadjuvant hormone therapy were 95.8% and 81.7%. respectively. Acute-phase adverse events (NCI/CTCAE) were observed in 32 patients (60.4%), and all were grade 1 or 2. No late adverse events were observed. CONCLUSION: IMRT is possible treatment for localized and locally advanced prostate cancer without high-grade toxicity. We continue to evaluate the efficacy and durability of IMRT.

[Invasive bladder cancer with concomitant carcinoma in situ treated with chemoradiotherapy followed by BCG intravesical infusion therapy to preserve the bladder : report of three cases].

Three patients with invasive bladder cancer and concomitant carcinoma in situ were treated sequentially with chemoradiotherapy followed by BCG intravesical infusion therapy to preserve the bladder. Local complete response was achieved in all patients, although lymph node metastasis was noted in one patient. The multimodality therapy could be safely administered without acute or late complications, including decreased bladder capacity.

[A case of Fournier's gangrene in which Flexi-Seal was effective for evacuation management].

A 67-year-old male was referred to our hospital with septicemia from necrotizing fasciitis of the genitalia of unknown origin. He had a history of diabetes and cerebral infarction. Extensive debridement of necrotizing tissue was performed over an area extending from the lower abdomen to the light inguinal,scrotal and perianal regions. At a suitable point,Flexi-Seal was applied to the wound as a preventive measure against infection. There was no contamination of perianal wounds,allowing them to be closed without infection. The Flexi-Seal was successfully removed after around 3 weeks. This is the second case in which Flexi-Seal was used in Japan to treat Fourier's gangrene.

[A case of prostate cancer that developed following transurethral resection of the prostate: diagnostic efficiency of diffusion-weighted images on magnetic resonance imaging].

An 84-year-old man underwent transurethral resection of the prostate (TURP) with a diagnosis of prostatic hypertrophy at the age of 78. He had a moderately high prostate specific antigen (PSA) level of 4.5 ng/ml before TURP, but without pathological malignancy. Following surgery, his PSA level dropped to 1.7 ng/ml and the patient recovered almost completely. Four years later, however, he underwent a reexamination due to diminished urinary flow. His PSA at that time was 5.2 ng/ml, continuing to rise slowly thereafter. Six years following surgery, his PSA reached 13.7 ng/ml, and the diffusion-weighted image on magnetic resonance imaging showed a high intensity area in the prostatic portion of the urethra. A poorly differentiated adenocarcinoma was detected in TUR-derived tissue fragments of the tumor protruding from the prostate. Tissue obtained via a systematic needle biopsy showed no signs of malignancy. Hormonal therapy was introduced. Five months later, the PSA level fell to 0.130 ng/ml ; the patient is now in clinical follow-up.

[A case of infiltrating transitional cell carcinoma of kidney difficult to distinguish from xanthogranulomatous pyelonephritis].

The patient, a 67-year-old man, initially visited another institution with asymptomatic macroscopic hematuria as the major complaint. Since imaging revealed a tumor occupying the left kidney, he was referred to our hospital. Computed tomography (CT) was suggestive of a tumor involving the renal pelvis that had infiltrated the renal parenchyma. The patient was scheduled for surgery, which was postponed when pre-operative CT indicated a reduction in the tumor size, leading to a subsequent diagnosis of xanthogranulomatous pyelonephritis. Surgery was eventually conducted to address complaints such as persistent hematuria. The pathological diagnosis was infiltrating transitional cell carcinoma of the kidney. Urinary cytodiagnoses were class II-III throughout the observation period.

[A case of urinary incontinence due to hypoplastic kidney with an ectopic ureteral opening: successful treatment with transcatheter arterial embolization].

We report a 21-year-old woman,who presented with a major complaint of urinary incontinence without dry time. On the basis of computed tomographic examination and vaginography,she was diagnosed as having a hypoplastic left kidney with a solitary ectopic ureteral opening on the left. Transcatheter arterial embolization of the renal artery using anhydrous ethanol was conducted for renal ablation. No postoperative complications were noted,and the symptoms of urinary incontinence were eliminated. Embolization of the renal artery for ablation of a hypoplastic kidney with symptoms can be achieved without laparotomy while causing little stress and few complications,with an outcome comparable to surgical nephrectomy. This procedure is expected to be adopted as a standard therapeutic modality in the future.

Reactivation of latent tuberculosis infection induced by cabazitaxel in a patient with prostate cancer: A case report.

RATIONALE: Latent tuberculosis infection (LTBI) describes the dormant state of tuberculosis (TB), in which persistent immune-related interaction between TB and T-cells maintain its state. Cabazitaxel (CBZ) is reported to improve overall survival in patients with castration-resistant prostate cancer (CRPC) after progression observed in regimens including docetaxel. CBZ is known for severe myelosuppression; however there is no recommendation for the treatment of LTBI before CBZ treatment. To the authors' knowledge, this is the first report to describe reactivation of LTBI induced by CBZ. PATIENT CONCERNS: A 75-year-old Japanese male with a medical history of TB since 16 years of age had been treated for prostate cancer (PC) (initial prostate-specific antigen 532 ng/ml; cT4N1M1b; Gleason score4+4) with androgen deprivation therapy, abiraterone, and docetaxel. Calcified nodules and radiological findings of LTBI were present in the upper right lobe since the diagnosis of PC. After progression was observed during these treatments, CBZ was administered combined with pegfilgrastim, long-acting granulocyte colony-stimulating factor (G-CSF). Seven days after the third course of CBZ, he was admitted to the authors' hospital to treat febrile neutropenia (FN). High fever persisted even after myelosuppression had recovered. Computed tomography (CT) revealed distribution of small nodules in the bilateral lungs, for which miliary TB was included in the differential diagnosis. T-Spot, interferon-gamma-release assay, and bronchoscopy yielded no significant findings; however, sputum and urine culture confirmed the diagnosis of TB. DIAGNOSIS: CT, sputum and urine culture confirmed the diagnosis of miliary TB. INTERVENTIONS: The patient was treated with anti-bacterial therapy (cefepime) on hospital admission, which was not effective. After the diagnosis of miliary TB was confirmed, anti-TB drugs, including isoniazid, rifampicin, pyrazinamide and ethambutol, were administered. OUTCOMES: Despite anti-TB therapy, high fever persisted and radiological findings worsened. Fifty days after the third course of CBZ, the patient died of respiratory dysfunction caused by progression of miliary TB. LESSONS: Management of LTBI is needed in cases of radiographic findings of LTBI and medical history of TB before CBZ treatment, despite the rarity of LTBI reactivation in patients with PC.

The Effect of intravitreal N-methyl-DL-aspartic acid on the electroretinogram in Royal College of surgeons rats.

PURPOSE: To investigate how the third-order neuronal response contributes to shaping the electroretinogram (ERG) in the Royal College of Surgeons (RCS) rat. METHODS: Full-field ERGs were recorded from dystrophic RCS rats (n = 30) at 4, 6, 8, 10, 12, or 14 weeks of age in response to different stimulus intensities (maximum intensity, 0.84 log cd-s/m(2)). N-methyl-DL: -aspartic acid (NMDA, 5 mM) was injected into the vitreous cavity of the right eyes to eliminate the third-order neuronal response. The left eyes received the vehicle and served as controls. The third-order neuronal response was isolated by digitally subtracting waveforms of the NMDA-injected eyes from those of the control eyes. RESULTS: The ERG a- and b-waves deteriorated with the age of the rat. The third-order neuronal response was preserved to a greater degree than the b-wave despite progression of photoreceptor degeneration. Intravitreal injection of NMDA attenuated the a-wave and enhanced the b-wave across the stimulus range from low to middle intensities. This tendency became more pronounced with advancing rat age. In aged dystrophic RCS rats this phenomenon was seen even at maximum intensity. The difference between NMDA-injected and vehicle-injected eyes was larger for the threshold than for the maximum amplitude at each examined time point (P < 0.001). Intravitreal injection of NMDA decreased implicit times of the a- and b-waves after the rats reached 8 weeks of age (P < 0.005 for the a-wave). CONCLUSION: With advancing photoreceptor degeneration, the third-order neuronal response made a greater contribution to shaping the a- and b-waves in dystrophic RCS rats.

Protective effect of hepatocyte growth factor against degeneration of the retinal pigment epithelium and photoreceptor in sodium iodate-injected rats.

PURPOSE: To investigate the possible protective effect of hepatocyte growth factor (HGF) against degeneration of photoreceptors and retinal pigment epithelium (RPE) in vivo. METHODS: Sprague-Dawley (SD) rats received an intravitreal injection of HGF in the right eye. The left eye was injected with vehicle as a control. Two days after the intravitreal injections, rats were administered 40 mg/kg of sodium iodate (NaIO3) intravenously. Scotopic ERGs were elicited by different stimulus intensities with a maximum luminance of 0.84 log cds/m2. To evaluate RPE function, the azide response was evoked by intravenous injection of 0.1 mg sodium azide. These electrophysiological measurements were conducted on days 4, 7, 14, and 28 after the NaIO3 injections. After recording ERGs or azide response, animals were sacrificed for quantification of the histological change and immunohistochemical analysis using antibodies against RPE 65. RESULTS: The threshold for the scotopic b-wave was significantly lower in HGF-treated eyes than in untreated control eyes (p < 0.005), and maximum b-wave amplitudes (Vbmax) were significantly larger in HGF-treated eyes (p < 0.05) across all experimental time points after NaIO3 injection. Azide response amplitudes were significantly larger in the HGF-treated eyes than in the untreated eyes (p < 0.05). The structure of the outer retina was preserved to a greater degree in the HGF-treated eyes than in the untreated eyes (p < 0.05). Immunohistochemical analysis demonstrated that irregular alignment of the outer nuclear layer was confined to the retinal area that was not stained with RPE 65. CONCLUSIONS: Our results indicated that an intravitreal injection of HGF provided significant protection against degeneration of the photoreceptor and RPE induced by systemic administration of NaIO3. This suggests that HGF could be used as a therapeutic agent for degeneration of photoreceptors as well as RPE.