Hypertensive cerebral hemorrhage with undetectable plasma vascular endothelial growth factor levels in a patient receiving intravitreal injection of aflibercept for bilateral diabetic macular edema: a case report.

BACKGROUND: Intravitreal injections of anti-vascular endothelial growth factor are commonly used to treat macular diseases, including diabetic macular edema. Anti-vascular endothelial growth factor drugs can enter the systemic circulation after intravitreal injections and appear to suppress circulating vascular endothelial growth factor levels. However, whether this can cause any systemic adverse events remains unknown. CASE PRESENTATION: A 70-year-old Japanese man diagnosed with diabetic macular edema in both eyes was treated with anti-vascular endothelial growth factor intravitreal injections. One month after receiving two intravitreal injections of aflibercept 1 week apart for diabetic macular edema in both eyes, he complained of a severe acute headache. The patient was diagnosed with hypertensive cerebral hemorrhage of the occipital lobe based on an elevated blood pressure of 195/108 mmHg and the results of computed tomography and magnetic resonance imaging of his brain. The patient was treated with an intravenous injection of nicardipine hydrochloride to lower his systemic blood pressure. Two days after the stroke, the patient began oral treatment with 80 mg/day telmisartan, which was continued for 3 days, and the telmisartan dose was reduced to 40 mg/day thereafter. His blood pressure promptly dropped to 130/80 mmHg, and his severe headache disappeared. One year after the cerebrovascular stroke, the telmisartan was discontinued because his blood pressure stabilized at a normal level. His plasma vascular endothelial growth factor levels were measured via specific enzyme-linked immunosorbent assay before and after the intravitreal injections of aflibercept. Immediately before the injections, the vascular endothelial growth factor level was 28 pg/ml, but it rapidly fell below the detection limit within 1 week, where it remained for over 2 months. Two days before the cerebral hemorrhage, his plasma vascular endothelial growth factor level was below the detection limit, and 2 months later after the stroke, his plasma vascular endothelial growth factor level recovered to 41 pg/ml. CONCLUSION: This case suggests that hypertension and resultant cerebral hemorrhage can occur in patients with diabetic macular edema when plasma vascular endothelial growth factor levels are systemically decreased below the detection limit for a prolonged time after local injections of anti-vascular endothelial growth factor agents into the vitreous cavity. Therefore, severely reduced plasma vascular endothelial growth factor levels could be a higher risk factor to develop generally infrequent stroke. Ophthalmologists should be aware of possible severe reduction of plasma vascular endothelial growth factor levels and resultant increase in blood pressure after intravitreal injections of an anti-vascular endothelial growth factor drug. If the plasma vascular endothelial growth factor levels could be monitored more easily and quickly during the treatment, it would help to prevent adverse events.

A case of proliferative diabetic retinopathy that regressed on human immunodeficiency virus treatment.

We report the case of a patient with proliferative diabetic retinopathy, who was later found to have human immunodeficiency virus infection that progressed rapidly. However, we could not determine the clinical course after the onset of human immunodeficiency virus because the patient died shortly after it was detected. In this patient, the activity of proliferative diabetic retinopathy showed regression after treatment for human immunodeficiency virus was initiated.

Occult macular dystrophy with bilateral chronic subfoveal serous retinal detachment associated with a novel RP1L1 mutation (p.S1199P).

PURPOSE: The purpose of this study was to present an atypical case of occult macular dystrophy (OMD) with bilateral chronic subfoveal serous retinal detachment (SRD). METHODS: A 53-year-old man was ophthalmologically evaluated because of decreased visual acuity in both eyes. Genomic DNA was extracted from venous blood samples. Mutational analysis of the retinitis pigmentosa 1-like 1 (RP1L1) gene was performed by Sanger sequencing. RESULTS: Best-corrected visual acuity (BCVA) was 0.1 logMAR in both eyes until the age of 53, after which it gradually declined. Full-field electroretinography (ERG) was unremarkable, while multifocal ERG revealed a reduced central response in both eyes. Optical coherence tomography showed subfoveal SRD in both eyes, and fundus fluorescein angiography yielded unremarkable results. His brother and cousin had similar subjective symptoms. At age 58, his logMAR BCVA was 0.532 (OD) and 0.347 (OS). He was given 23 administrations of intravitreal bevacizumab (IVB; 1.25 mg) in both eyes alternately over a 2-year period and also underwent reduced-fluence photodynamic therapy in both eyes. Two years after the first administration of IVB, a reduction in SRD was obtained, and IVB was therefore discontinued. Three years after the first administration, logMAR BCVA was 0.155 (OD) and 0.523 (OS). Mutational analysis revealed a novel heterozygous missense mutation (p.S1199P). CONCLUSIONS: We describe in detail a case of bilateral chronic subfoveal SRD in an atypical OMD patient carrying a novel heterozygous RP1L1 mutation (p.S1199P). Our results further extend the phenotypic spectrum of RP1L1-associated OMD.

Experience using the heidelberg retina angiograph 2 with a wide-field contact lens system in diabetic retinopathy cases.

INTRODUCTION: HRA (Heiderberg Retina Angiograph) 2 uses a confocal scanning laser system which can provide high quality digital images but its imaging field is only 30°at most. HRA2 with a wide-field contact lens system allows an imaging field of up to 150°. METHODS: We examined the advantages and disadvantages of HRA2, with a wide-field contact lens, for the evaluating diabetic retinopathy (DR). RESULTS: HRA2 was beneficial for obtaining images of the entire retina simultaneously, without missing peripheral retinal non-perfusion and neovascularization. On the other hand, clear images connot be acquired in cases with media opacities such as corneal dystrophy, cataract and asteroid hyalosis, or in those with yellow tinted IOL. CONCLUSIONS: HRA2 with a wide-field contact lens is useful for visualizing peripheral retinal lesions in DR cases.

[Changes in diabetic retinopathy and visual acuity in patients with end-stage diabetic nephropathy after the introduction of hemodialysis].

PURPOSE: To study the diabetic retinopathy (DR) and visual acuity in patients with end-stage diabetic nephropathy in the predialysis period and the changes after the initiation of hemodialysis at Tokyo Postal Service Agency Hospital (TPSAH). METHODS: We retrospectively analyzed the systemic conditions and the stage of DR and visual acuity in the medical records, of 24 patients 48 eyes (male: female=20 : 4) with diabetic nephropathy, who were started on hemodialysis between June 1994 and August 2003 at TPSAH, and were followed ophthalmologically more than 6 months after the start of hemodialysis. RESULTS: At the start of hemodialysis, 46 of 48 eyes (95.8%) had already been treated by retinal photocoagulation. The DR activity was assessed as "low" in 62.5% of the patients at the start of hemodialysis, but 6 months later, over 95% of the patients were assessed as having "low-activity". At the start of hemodialysis visual acuity was less than 0.1 in 21% of the eyes, and over 0.7 in 42% of the eyes, and the ratio was stable in the follow-up period. In 2 eyes the stage of diabetic retinopathy became worse by more than one grade in Fukuda's grading of diabetic retinopathy, and in 4 eyes more than a 2 grade alteration in visual acuity was observed. CONCLUSIONS: After the start of hemodialysis, DR became less active relatively early, and only a few eyes became worse in visual acuity and DR.

Orbital varix rupture during cataract surgery.

We report a case of orbital varix rupture during cataract surgery with retrobulbar anesthesia. No remarkable changes were observed 10 minutes after retrobulbar anesthesia was administered, but a rise in intraocular and intraorbital pressure was noted about 10 minutes after phacoemulsification began. The eyelid could not be closed at the end of surgery because of severe proptosis. Follow-up by magnetic resonance imaging and color Doppler imaging revealed orbital hemorrhage and varix. Based on the time of its appearance, the hemorrhage was thought to be the result of venous congestion caused by anesthetic agent in the muscle cone. Although intermittent exophthalmos is a symptom of orbital varix, silent orbital varix should be considered when selecting the method of anesthesia for ocular surgery.