Time to development of ocular syphilis after syphilis infection.

To provide an estimate of the incubation period of ocular syphilis based on serology using both clinical data and stored serum samples, we retrospectively reviewed patients with HIV-1 infection who presented with ocular syphilis between August 1997 and July 2015 in a tertiary hospital in Japan. The incubation period of ocular syphilis was defined as the time from syphilis infection to the development of ocular symptoms due to ocular syphilis. During the study period, 20 patients were diagnosed with ocular syphilis and 8 patients were enrolled in the present study. All patients were Japanese men who have sex with men with a median age of 46 years (IQR 41.5-53.5). The median CD4 count was 668.5/µL (IQR 567.8-734.3) and 5 of the 8 patients had HIV-1 viral load of less than 50 copies/mL. All study patients presented to our clinic because of the development of ocular symptoms, and they did not have any other symptoms compatible with primary, secondary, or tertiary syphilis. The median time between syphilis infection and development of ocular symptoms was 11 months (IQR 4-19, range 2.5-45). Seven out of eight (87.5%) cases developed ocular syphilis within 2 years of syphilis infection. Ocular syphilis should be suspected even in patients with early syphilis who present with ocular symptoms. Moreover, routine serologic screening for syphilis among patients with HIV-1 infection is critical for prevention of irreversible visual loss in ocular syphilis cases.

Higher Numbers of Hyperreflective Foci Seen in the Vitreous on Spectral-Domain Optical Coherence Tomographic Images in Eyes with More Severe Diabetic Retinopathy.

PURPOSE: The aim of this study was to determine whether spectral-domain optical coherence tomography (SD-OCT) can detect and quantify the number of hyperreflective foci attached to the retina and in the vitreous of patients at different stages of diabetic retinopathy (DR). METHODS: The medical charts of 929 eyes of 465 patients who had undergone SD-OCT were reviewed. The number of hyperreflective foci in the vitreous and attached to the retina was determined in the SD-OCT images. RESULTS: Of the 929 eyes, 284 eyes from diabetic patients and 265 eyes from controls met the inclusion criteria. The number of hyperreflective foci increased significantly as the severity of DR increased. CONCLUSIONS: The correlation between the average number of hyperreflective foci and the severity of DR indicates that quantifying the number of hyperreflective foci may be used to estimate the severity of DR and, thus, identify eyes which require further tests or treatments.

Reduced serum level of leukocyte cell-derived chemotaxin 2 is associated with the presence of diabetic retinopathy.

BACKGROUND: Vascular endothelial growth factor (VEGF) signaling is an important pathway in the development of diabetic retinopathy (DR). A recent report showed that leukocyte cell-derived chemotaxin 2 (LECT2) suppresses the VEGF signaling in endothelial cells. However, the clinical relevance of LECT2 in DR is unknown. This study aimed to investigate serum LECT2 levels and the presence of DR. METHODS: The study included 230 people with type 2 diabetes mellitus (DM), 95 with DR and 135 without DR. Serum LECT2 levels were measured using an enzyme-linked immunosorbent assay. Data were evaluated using Spearman's rank correlation, univariate and multivariate logistic regression. RESULTS: Serum LECT2 levels were significantly lower in participants with DM having DR than in those not having DR (35.6±14.9ng/ml vs. 44.5±17.6ng/ml, P<0.001). Spearman's rank correlation analysis revealed a significant association between serum LECT2 levels and the presence of DR (P<0.001). Multiple regression analysis revealed that serum LECT2 levels were independently related to DR (P<0.001). CONCLUSIONS: These findings indicated that serum LECT2 level is negatively associated with the presence of DR and suggest that low circulating LECT2 level is a risk factor for DR.

Ophthalmic Manifestations of Hematopoietic Malignancy.

Purpose. To report the ocular findings in patients with hematopoietic malignancy with optic nerve involvement and abducens nerve palsy. Methods. The medical records of all cases of hematopoietic cancer with ophthalmic involvements seen in the Department of Ophthalmology of the National Center for Global Health and Medicine between 2009 and 2014 were reviewed. Results. Eight patients with hematopoietic cancer with optic nerve invasion or abducens nerve palsy were studied. The primary diseases were 3 cases of multiple myeloma, 1 case of acute lymphocytic leukemia, 1 case of follicular lymphoma, and 3 cases of AIDS-related lymphoma. Six cases had optic nerve invasion, 2 cases had abducens nerve palsy, and 1 case had optic nerve invasion of both eyes. The median visual acuity of eyes with optic nerve invasion was 0.885 logarithm of the minimum angle of resolution (logMAR) units. The final visual acuity of eyes with optic nerve invasion was 1.25 logMAR units, and that of those with sixth-nerve palsy was -0.1 logMAR units. Six cases died during the five-year follow-up period. An ophthalmic involvement in patients with hematopoietic cancer, especially AIDS-related lymphoma, was associated with poor prognosis. Conclusion. Because ophthalmic involvement in patients with hematopoietic malignancy has a poor prognosis, an early diagnosis of the cancers by the ophthalmologic findings by ophthalmologists could improve the prognosis.

Prognosis of ocular syphilis in patients infected with HIV in the antiretroviral therapy era.

OBJECTIVE: To describe the clinical course and prognosis of ocular syphilis in patients infected with HIV-1 in the antiretroviral therapy (ART) era. METHODS: We conducted a single-centre retrospective chart review of ocular syphilis in patients infected with HIV-1 diagnosed between August 1997 and July 2015. The prognosis of best-corrected visual acuity (BCVA) was analysed. RESULTS: The study subjects were 30 eyes of 20 men who had sex with men (MSM) (median age, 41). Loss of vision and posterior uveitis were the most common ocular clinical features (43%) and location of inflammation at presentation (50%), respectively. The median baseline BCVA was 0.4 (IQR 0.2-1.2), including three eyes with hand motion. BCVA≤0.4 at diagnosis was significantly associated with posterior uveitis or panuveitis (p=0.044). Seventy-five per cent were treated with intravenous benzylpenicillin and 53% were diagnosed with neurosyphilis. After treatment (median follow-up: 21 months), BCVA improved in 89% of the eyes, including all eyes with hand motion, to a median BCVA of 1.2 (IQR 0.8-1.2). Kaplan-Meier analysis showed that >28 days of ocular symptoms before diagnosis was the only factor associated with poor prognosis of BCVA. Three patients (15%) developed recurrence after treatment. CONCLUSIONS: The prognosis of BCVA in HIV-infected patients with ocular syphilis in the ART era was favourable after proper treatment. Having >28 days of ocular symptoms before diagnosis was associated with poor prognosis. Changes in visual acuity in HIV-infected MSM should prompt an immediate assessment for ocular syphilis as delays in diagnosis and therapy can lead to irreversible visual loss.

Routine Eye Screening by an Ophthalmologist Is Clinically Useful for HIV-1-Infected Patients with CD4 Count Less than 200 /µL.

OBJECTIVE: To investigate whether routine eye screening by an ophthalmologist in patients with HIV-1 infection is clinically useful. METHODS: A single-center, retrospective study in Tokyo, Japan. HIV-1-infected patients aged over 17 years who visited our clinic for the first time between January 2004 and December 2013 and underwent full ophthalmologic examination were enrolled. At our clinic, ophthalmologic examination, including dilated retinal examination by indirect ophthalmoscopy was routinely conducted by ophthalmologists on the first visit. The prevalence of ophthalmologic diseases and associated factors including the existence of ocular symptoms were analyzed. RESULTS: Of the 1,515 study patients, cytomegalovirus retinitis (CMV-R) was diagnosed in 24 (2%) patients, HIV retinopathy (HIV-R) in 127 (8%), cataract in 31 (2%), ocular syphilis in 4 (0.3%), and uveitis with unknown cause in 8 (0.5%). Other ocular diseases were diagnosed in 14 patients. The CD4 count was <200 /µL in all CMV-R cases and 87% of HIV-R. The prevalence of any ocular diseases, CMV-R, and HIV-R in patients with CD4 <200 /µL were 22%, 3%, and 15%, respectively, whereas for those with CD4 ≥200 /µL were 5%, 0%, and 2%, respectively. No ocular symptoms were reported by 71% of CMV-R cases and 82% of patients with any ocular diseases. CONCLUSIONS: Routine ophthalmologic screening is recommended for HIV-1-infected patients with CD4 <200 /µL in resource-rich settings based on the high prevalence of ocular diseases within this CD4 count category and because most patients with ocular diseases, including those with CMV-R, were free of ocular symptoms.

[Multimodal imaging of a case of acute syphilitic posterior placoid chorioretinitis].

BACKGROUND: Acute syphilitic posterior placoid chorioretinitis (ASPPC) is a rare manifestation of ocular syphilis. We report on multimodal imaging including ophthalmoscopy, spectral-domain optical coherence tomography (SD-OCT), fluorescein angiography (FA) and indocyanine green angiography (IA) of a case diagnosed with ASPPC. CASE: A 45-year-old man who was positive for human immunodeficiency virus presented with a 2-week history of visual loss in the right eye. CLINICAL FINDINGS: Ophthalmoscopy showed a unilateral yellowish lesion involving the macula. SD-OCT revealed absence of the photoreceptor inner segment ellipsoid as well as an absent external limiting membrane, and nodular elevations of the retinal pigment epithelium layer at the macula. Late IA demonstrated punctate hypofluorescent dots in diffuse hyperfluorescent area corresponding to the macular lesion. Serologic tests were positive for syphilis and the patient was treated with intravenous penicillin G. Visual acuity improved with treatment from 20/100 to 20/16 and the retinal appearance returned to normal. There was completely restored stratification of the outer retina after therapy. CONCLUSION: In the present case of ASPPC, the SD-OCT imaging demonstrated characteristic abnormalities including RPE nodularity which showed hypofluorescent dots on late IA.

Diagnostic utility of quantitative plasma cytomegalovirus DNA PCR for cytomegalovirus end-organ diseases in patients with HIV-1 infection.

OBJECTIVE: To investigate the diagnostic value of quantitative plasma cytomegalovirus (CMV)-DNA polymerase chain reaction (PCR) for CMV end-organ diseases (CMV-EOD) in patients with HIV-1 infection. DESIGN: Single-center cross-sectional study. METHODS: The study subjects were HIV-1-infected patients with CD4 ≤200 per microliter, who had undergone ophthalmologic examination with plasma CMV-DNA PCR measured within 7 days. CMV retinitis and other CMV-EOD were diagnosed according to the ACTG criteria. PCR value was converted into the WHO international standard. RESULTS: CMV retinitis and all CMV-EOD were diagnosed in 23 (5%) and 37 (8%) of the 461 study patients, respectively. CMV-DNA was undetectable (<185 IU/mL) in 2 patients with CMV retinitis and 1 with encephalitis. The area under the receiver operating characteristic curve of CMV-DNA for CMV retinitis and all CMV-EOD were 0.80 [95% confidence interval (CI): 0.71 to 0.89] and 0.82 (0.75 to 0.89), respectively. The sensitivity, specificity, positive predictive value, and negative predictive value for each cutoff value of CMV-DNA were as follows: for CMV retinitis, ≥10,086 IU/mL: 26.1%, 94.1%, 18.8%, 96%; ≥2946 IU/mL; 56.5%, 86.8%, 18.3%, 97.4%; ≥959 IU/mL; 60.9%, 78.1%, 12.7%, 97.4%; detectable CMV-DNA (≥185 IU/mL): 91.3%, 48.2%, 8.5%, 99.1%; for all CMV-EOD: ≥10,086 IU/mL: 32.4%, 95.3%, 37.5%, 94.2%; ≥2946 IU/mL; 54.1%, 88%, 28.2%, 95.6%; ≥959 IU/mL; 62.2%, 79.5%, 20.9%, 96%; detectable CMV-DNA; 91.9%, 49.5%, 13.7%, 98.6%. CONCLUSIONS: Plasma CMV-DNA PCR has a high diagnostic value for both CMV retinitis and all CMV-EOD in patients with advanced HIV-1 infection. A cutoff value of CMV-DNA ≥10,086 IU/mL and ≥2946 IU/mL yields high specificity, whereas undetectable CMV-DNA load (<185 IU/mL) likely rules out CMV-EOD.

Relation of intraocular concentrations of inflammatory factors and improvement of macular edema after vitrectomy in branch retinal vein occlusion.

PURPOSE: To investigate the association of intraocular concentrations of inflammatory factors and improvement of macular edema after vitrectomy for patients with macular edema in branch retinal vein occlusion (BRVO). DESIGN: Retrospective case-control study. METHODS: Seventeen patients with BRVO who underwent vitreous surgery for macular edema and 15 control patients were enrolled from Hachioji Medical Center of Tokyo Medical University. The concentrations of eight inflammatory factors were measured in vitreous and aqueous fluids obtained at the time of vitrectomy using a flow cytometer. Macular thickness was measured by optical coherence tomography before and one, three, and six months after surgery. Correlations between the concentrations of inflammatory factors and macular thickness were statistically analyzed. RESULTS: Higher aqueous and vitreous concentrations of vascular endothelial growth factor (VEGF) and interleukin (IL)-8 were significantly correlated with a greater difference in macular thickness between before and six months after surgery (vitreous VEGF, P=.047; aqueous VEGF, P=.032; vitreous IL-8, P=.016; and aqueous IL-8, P=.032). Higher intraocular concentrations of monokine induced by interferon γ (Mig) were significantly correlated with a smaller degree of macular thickness six months after surgery (vitreous Mig, P=.038; aqueous Mig, P=.009). CONCLUSION: High preoperative VEGF, IL-8, and Mig concentrations were associated with improvement of macular edema six months after vitreous surgery in patients with macular edema attributable to BRVO.

Decreased retinal neuronal cell death in caspase-1 knockout mice.

PURPOSE: To determine whether apoptosis of retinal neurons induced by excessive light exposure and ischemia-reperfusion injury is altered in caspase-1 knockout mice. METHODS: Eight- to 10-week-old caspase-1 knockout mice (Casp1-/-) and wild-type (WT) mice (C57BL/6) were exposed to diffuse, cool, white fluorescent light of 25,000 lux for 2 h. Other mice were subjected to retinal ischemia by increasing the intraocular pressure to 110 mmHg for 45 min. Electroretinograms (ERGs) were recorded before and after the light exposure. TdT-dUTP terminal nick-end labeling (TUNEL) was performed to identify the apoptotic cells after the insults. The inner retinal thickness was measured to evaluate the retinal injury after the ischemia-reperfusion. Expression of caspase-1 protein was studied by immunohistochemical analysis and Western blotting. Caspase-1-like protease activity was determined by a colorimetric tetrapeptide substrate. RESULTS: The morphology of the retina and the amplitudes of the a and b waves of the ERGs of Casp1-/- mice did not differ from those of WT mice. After the light exposure, TUNEL-positive cells were observed in the outer nuclear layer of the WT mice retina. The number of TUNEL-positive photoreceptor nuclei after the light exposure, and the number of nuclei in the inner nuclear layer after the ischemia-reperfusion injury, were significantly less in Casp1-/- mice than in WT mice. There were more caspase-1-positive photoreceptor cells in WT mice after the light injury. The inner retinal layer of Casp1-/- mice was significantly thicker in Casp1-/- mice than in WT mice 2 weeks after the ischemic insult. CONCLUSIONS: Retinal neuronal apoptosis was less prominent in Casp1-/- mice after excessive light exposure and ischemia-reperfusion injury. These data indicate that caspase-1 plays a role in retinal neuronal apoptosis.

Rubeosis iridis after bilateral cataract surgery and its spontaneous regression in a patient with myotonic dystrophy.

A 49-year-old cataract patient with myotonic dystrophy had phacoemulsification and intraocular lens implantation in both eyes. Rubeosis iridis developed bilaterally 10 days later and began to regress without treatment 2 weeks after the surgery. It was completely absent 1 year after the surgery. These findings indicate that surgeons should be aware that rubeosis iridis can develop in myotonic patients after cataract surgery.

Expression of c-Jun and Bcl-2 family proteins in apoptotic photoreceptors of RCS rats.

PURPOSE: To determine if c-Jun and Bcl-2 family proteins play a role in photoreceptor apoptosis in Royal College of Surgeons (RCS) rats. METHODS: RCS and Sprague-Dawley rats were used. Cryosections of retinas harvested at various postnatal periods were immunostained with antibodies against c-Jun, Bcl-2, and Bax. Double staining with TdT-dUTP nick-end labeling (TUNEL) or propidium iodide (PI) and antibodies was also done. To study the time course of gene and protein expression, semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblotting analyses were carried out. RESULTS: TUNEL-positive photoreceptors of RCS rats were stained strongly with antibodies against c-Jun and Bax. The number of immunoreactive cells increased on days 21 and 28 after birth (P21 and P28) and decreased on P45. Semiquantitative RT-PCR analysis showed that mRNAs for c-Jun and Bax were upregulated at P21 and P28, but those for Bcl-2 were unchanged. On immunoblotting, a 43-kDa band was revealed by the anti-c-Jun antibody and a 21-kDa band, by the anti-Bax antibody. Protein expression of c-Jun and Bax were increased at both P21 and P28. The temporal profiles of immunoreactivity, protein expression, and mRNA expression were similar. CONCLUSION: c-Jun and Bax may play a role in photoreceptor apoptosis in RCS rats.

Heme oxygenase-1 induced in muller cells plays a protective role in retinal ischemia-reperfusion injury in rats.

PURPOSE: To investigate the protective roles played by heme oxygenase (HO)-1 and -2 in the rat retina after ischemia-reperfusion injury. METHODS: Retinal ischemia was induced in rats by increasing the intraocular pressure to 110 mmHg for 60 minutes. The expression of HO-1 and -2 in the retina was determined by Western blot, real-time polymerase chain reaction (PCR), and immunohistochemistry. To inhibit the upregulation of HO-1, short interfering (si)RNA of HO-1 was injected intravitreally before ischemia and that of green fluorescent protein (GFP) was used as the control. Muller cell damage was assessed by counting the number of S-100-positive cells. The number of macrophages invading the retina was determined by counting the number of ED-1-positive cells. RESULTS: The expression of HO-1 mRNA and protein was upregulated at 6 hours after reperfusion and peaked at 12 to 24 hours, whereas that of HO-2 was not altered. HO-1 immunoreactivities were detected in Muller cells at 24 hours after reperfusion, and HO-2 immunoreactivities were detected in retinal cells. The HO-1 expression in the retina treated with siRNA of HO-1 was reduced at 12 and 24 hours after reperfusion compared with that injected with siRNA of GFP. The number of S-100-positive cells at 24 hours after reperfusion decreased significantly in retinas treated with HO-1 siRNA (P <0.01). The number of macrophages that had infiltrated the retina was increased in retinas pretreated with the siRNA of HO-1 compared with those treated with siRNA of GFP. On day 14 after reperfusion, HO-1 siRNA-treated retinas showed severe retinal injury and destruction of the retinal architecture. CONCLUSIONS: HO-1 promotes the survival of Muller cells after ischemia-reperfusion injury. Because inhibition of the upregulation of HO-1 resulted in an infiltration of inflammatory cells and destruction of the retina, the authors conclude that HO-1 induced in Muller cells plays a protective role in retinal ischemia-reperfusion.

Expression and neuroprotective effect of hepatocyte growth factor in retinal ischemia-reperfusion injury.

PURPOSE: To investigate the expression and possible neuroprotective effects of hepatocyte growth factor (HGF) in a rat model of retinal ischemia-reperfusion injury. METHODS: Retinal ischemia was induced in adult male Sprague-Dawley rats by raising the intraocular pressure to 110 mm Hg for 45 minutes. To study expression of HGF and its receptor c-Met, reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis, and immunohistochemical staining were performed on eyes enucleated at 6, 12, 24, 48, and 96 hours after reperfusion. To examine the neuroprotective effects of HGF, recombinant human (rh)HGF (1, 6, and 12 microg in 2 microL PBS) or vehicle was administered intravitreally 1 minute after reperfusion, and the eyes were enucleated at 6, 12, 24, 48, and 96 hours and 28 days after reperfusion. The retinal damage was assessed by electroretinogram (ERG) recordings, by measuring the inner retinal thickness, and by counting the number of TUNEL-positive cells in each retinal layer. RESULTS: RT-PCR and Western blot analyses showed upregulation of HGF and c-Met-HGF receptor mRNA at 6, 12, 24, and 48 hours after reperfusion, compared with the normal rat retina. Immunohistochemically, expression of HGF was found in the retinal pigment epithelial cells at 6 hours after reperfusion and in some cells in the ganglion cell layer and inner nuclear layer at 24 hours after reperfusion. The amplitudes of the ERG b-wave and oscillatory potentials were significantly larger in the eyes treated with 6 and 12 microg rhHGF than in those of vehicle-treated control rats (P < 0.01). On day 28, the thicknesses of the inner retina of vehicle-treated rats and that of 6-microg rhHGF-treated rats were 54.4 +/- 6.12 (mean +/- SD, n = 9) and 71.5 +/- 9.81 microm (n = 8), respectively (P < 0.01). The number of TUNEL-positive cells at 6, 12, 24, and 48 hours after reperfusion was decreased significantly by treatment with 6 microg rhHGF, compared with those in the control rats (P < 0.01). CONCLUSIONS: Upregulation of HGF in the retina may play a role in retinal ischemia-reperfusion injury. Intravitreal injection of rhHGF is neuroprotective against the injury.