Min-Muh Sheu

Anti-apoptotic effects of human granulocyte colony-stimulating factor (G-CSF) on retinal ganglion cells after optic nerve crush are PI3K/AKT-dependent

The purpose of present study is to dissect the role of PI3K/AKT signaling in the anti-apoptotic effects of human granulocyte colony-stimulating factor (G-CSF) on rat retinal ganglion cells (RGCs) after optic nerve (ON) crush. The ONs of seventy-two adult male Wistar rats were crushed by a standardized method. Control eyes received a sham operation. G-CSF or phosphate-buffered saline (PBS) was immediately administrated after the ON event for 5 days. Twelve rats were used to investigate the signaling pathways using western blot analysis. In other sixty rats, each eye also received intravitreal injections of PI3K/AKT inhibitor (LY294002) or PBS immediately after the experiments. Rats were euthanized at 1 or 2 weeks after the experiment. RGC density was counted by retrograde labeling with Fluorogold. Western blot analysis of p-AKT, TUNEL assays, and immunohistochemistry of the retinas were conducted. Two weeks after ON injury, RGC densities in the central and mid-peripheral retinas of ON-crushed, G-CSF treated rats were significantly higher than those of corresponding ON-crushed, G-CSF-treated and LY294002-injected rats (survival rates of 60% vs. 39% and 43% vs. 33%, respectively; p < 0.01). Decreased TUNEL staining and the up-regulations of p-AKT signaling in retinas of ON-crushed, G-CSF-treated rats were blocked by intravitreal injections of LY294002. The double staining showed that p-AKT expression co-localized with RGCs in the ON crushed, G-CSF treated retinas. In conclusion, the anti-apoptotic effects of G-CSF on RGCs are PI3K/AKT signaling dependent in the retinas to rescue RGCs after ON crush injury.

Comparisons of intraocular pressure measurements: Goldmann applanation tonometry, noncontact tonometry, Tono-Pen tonometry, and dynamic contour tonometry

AimsTo compare intraocular pressure (IOP) readings between Tono-Pen tonometry and GAT, between noncontact tonometry (NCT) and GAT, and between dynamic contour tonometry (DCT) and Goldmann applanation tonometry (GAT). The correlation between IOP reading and possible confounder was identified.MethodsThis observational cross-sectional study enrolled sixty-two healthy subjects. All IOP and ocular pulse amplitude (OPA) measurements were taken by a single ophthalmologist; mean keratometric power (MK), central corneal thickness (CCT), and lens thickness (LT) were measured by a single experienced technician.ResultsStepwise multiple regression analysis indicated that GAT (P=0.017) and DCT (P=0.002) readings correlated positively with MK; GAT, NCT, and Tono-Pen readings correlated positively with CCT (P<0.05); NCT (P=0.035), and DCT (P=0.016) readings correlated negatively with LT; GAT (P=0.006) and Tono-Pen (P=0.009) readings correlated positively with OPA.ConclusionsThe K, CCT, LT, and OPA are confounders in tonometry readings.

Acute Vision Loss after Intravitreal Injection of Bevacizumab (Avastin) Associated with Ocular Ischemic Syndrome

Aim: To report a patient with diabetic rubeosis who suffered from acute retinal ischemic change and stroke after intravitreal injection of bevacizumab. Methods: A 55-year-old man had diabetes with unilateral rubeosis and macular edema. Three days after receiving intravitreal injection of bevacizumab (1.25 mg in 0.1 ml), he developed acute vision loss and change of consciousness. A complete ocular examination, fluorescein angiography, carotid artery Doppler sonography and brain magnetic resonance imaging were performed. Results: Best corrected visual acuity before injection was 6/60 in the left eye. He had underlying left carotid artery stenosis combined with bilateral preproliferative diabetic retinopathy. Three days after intravitreal injection of bevacizumab, acute ocular ischemic syndrome occurred. He also suffered from acute stroke, and brain magnetic resonance angiography showed total left internal carotid artery occlusion. The final visual acuity was no light perception in the left eye and 3/6 in the right eye. Conclusions: Patients receiving intravitreal injections of bevacizumab should be evaluated for potential systemic risk factors such as carotid insufficiency, coagulopathy and poorly controlled diabetes mellitus. Acute ocular ischemic change may be associated with intravitreal injection of bevacizumab in patients with vascular compromised diabetic retinopathy and/or underlying stenosis of the carotid artery.

Screening amblyopia of preschool children with uncorrected vision and stereopsis tests in Eastern Taiwan.

Aims or purposeScreening for amblyopia at earliest age is important for early treatment and better prognosis. This study aimed at evaluating the validity of uncorrected distant and near visual acuity and random dot stereopsis for screening amblyopia.MethodsIn Eastern Taiwan, population-based screen tests were performed for children at age from 3 to 6 years. The tests included uncorrected distant and near visions and random dot stereopsis (300 s) test. The screen performers were registered nurses of local public health service posts. The golden standards of the tests were the results of examination by the ophthalmologists.ResultsIncluding Hans and aboriginal Taiwanese, 5232 children were included. Screened by distance visual acuity with different cutoffs and near visual acuity, 10.3, 30.3 and 8.2% children were abnormal. Screened by random dot, only 2% children were abnormal. By a senior ophthalmologist, 115 amblyopic children were diagnosed amblyopic. The sensitivities of distance visual acuity with low/high cutoff and near visual acuity were 74.7/84.8 and 49.4%, whereas that of the NTU random dot stereogram was 20.5%. Simultaneous testing of either two of the three tests improved the sensitivity.ConclusionScreening for amblyopia by the local nurses using the visual acuity tests or random dot stereopsis test alone does not display a high sensitivity. Simultaneous testing of distant visual acuity and stereopsis test elevate the sensitivity and preserve the specificity.

The current status of visual disability in the elderly population of Taiwan

PurposeThis study was conducted to explore the prevalence and the associated factors of visual impairment and blindness among the elderly Taiwanese population.MethodsA nationwide population-based visual health care screening program of elderly people aged 65 years or older was conducted between 1 July 2002 and 31 December 2002 in Taiwan. Based on the same standardized protocol used by the Bureau of Health Promotion, Department of Health, and a stratified random sampling design, 3160 out of 5000 elderly subjects were selected by a two-stage visual care screening method. The overall response rate was 63.2%.ResultsThe mean age of the elderly participants was 72.4 ± 5.1 years. The overall prevalence of glaucoma, corneal diseases, trauma, cataracts, myopic or diabetic retinopathy, and age-related macular degeneration among the elderly population was 2.1%, 6.3%, 0.9%, 60.2%, 7.5%, and 2.9%, respectively. The overall prevalence of visual disability (visual acuity of the better eye <0.5) was 17.7%, including 17.1% with visual impairment and 0.6% with blindness. Based on logistic regression, the significant independent factors of visual disability (visual impairment plus blindness) were sex (male vs. female, odds ratio (OR) = 0.62, 95% confidence interval (CI), 0.51–0.76), age (70–74 years vs. 65–69 years, OR = 1.60, 95% CI, 1.24–2.06; 75–79 years vs. 65–69 years, OR = 2.52, 95% CI, 1.92–3.32, ≥80 yrs vs. 65–69 yrs, OR = 4.86, 95% CI, 3.52–6.70), corneal diseases (OR = 2.26, 95% CI, 1.61–3.16), myopic or diabetic retinopathy (OR = 1.69, 95% CI, 1.20–2.39), age-related macular degeneration (OR = 4.96, 95% CI, 3.16–7.78), and cataract (OR = 3.40, 95% CI, 2.67–4.33).ConclusionsThe geographic difference in the prevalence of vision-related eye disease, visual impairment, and blindness point to the importance of taking actions that suit local circumstances. Our results also revealed that visual impairment and blindness are important visual health problems in the elderly Taiwanese population. Age-related macular degeneration, cataracts, corneal diseases, myopic or diabetic retinopathy, female sex, and aging were the leading causes of visual disability. Further organized preventive strategies for eye care are recommended in this population.

Treatment of Acanthamoeba Keratitis Combined With Fungal Infection With Polyhexamethylene Biguanide

From July 1996 to March 1997, three cases of Acanthamoeba keratitis combined with fungal infection were diagnosed and treated at our ophthalmic department. Specimens from all of these cases were obtained by corneal scraping, keratectomy and anterior chamber paracentesis. The diagnosis was confirmed by either the results of smear test or pathology reports. All of these patients received aggressive treatment with polyhexamethylene biguanide (PHMB) 0.02%, fluconazole, and anegyn eye drops. After the infection had been controlled without extension, therapeutic penetrating keratoplasty was performed on all of these patients despite the existence of infiltration beyond the edge of the graft. Postoperatively, eye drops were tapered gradually, and treatment was continued for 1 to 2 months. All three cases achieved good results and there was no recurrence of infection. Two cases had visual acuity of 20/100 and 20/20, while the other one perceived hand movement only due to later graft rejection. These cases suggest that early diagnosis and immediate use of PHMB and anti-fungal agents are effective in the treatment of Acanthamoeba keratitis combined with fungal infection.

Reproducibility of peripapillary retinal nerve fiber layer and macular retinal thickness measurements using optical coherence tomography.

We investigated the interoperator reproducibility of peripapillary retinal nerve fiber layer (RNFL) and macular retinal thickness measurements using optical coherence tomography (OCT) in healthy Taiwanese eyes. In this study, OCT‐3 was used by three trained and experienced operators to measure peripapillary RNFL and macular retinal thickness in a randomly chosen single eye from each normal subject. Mean thickness levels and the differences in thickness measurements among the three operators were calculated and compared. The eyes of 39 subjects (24 females and 15 males) were enrolled. The mean age of the subjects was 30.4 ± 16.1 years (range, 11‐46 years). The mean pupil diameter after pupillary dilation was 7.4 ± 0.6 mm (range, 6‐9 mm). Comparing peripapillary RNFL and macular retinal thickness measurements after pupillary dilation, there were no significant differences in: superior, inferior, temporal, and nasal peripapillary areas; 6 mm total macular volume and foveal thickness; and 1, 3 and 6 mm perifoveal areas among the three operators. In this study, OCT thickness measurements showed good interoperator reproducibility among three trained and experienced operators.

Fungal keratitis caused by Candida utilis--case report.

We report the first case of an ocular fungal infection caused by Candida utilis in a 72-year-old woman. Although candidiasis is the most common opportunistic fungal infection in humans, C. utilis had not been associated with human morbidity until two cases of fungemia were reported in 1988 and 1993. The clinical features exhibited typical feather-like infiltration at the ulceration margin of this case. After treatment with topical fluconazole and amphotericin-B, the ulceration healed within 3 weeks. The patient underwent penetrating keratoplasty and regained useful vision. We concluded that C. utilis is a new corneal pathogen and should be included in the differential list of mycotic keratitis.

Etiology of ocular diseases in elderly Amis aborigines in Eastern Taiwan (The Amis Eye Study).

PurposeTo determine the incidence of and risk factors associated with major ocular diseases in the elderly Amis population of Taiwan.MethodsThis population-based cross-sectional study is the most current survey of ocular diseases among elderly Amis. The overall response rate was 61.2%, with 2316 participants screened. All ocular examinations were performed using a mobile ophthalmology setup staffed by an ophthalmologist with 30 years of experience.ResultsThe mean age of the participants was 71.65 years. Cataracts were the most common ocular disease (82.6%), followed by pterygium (44.1%), arteriosclerotic changes in retinal vessels (35.7%), hypertensive retinopathy (18.5 %), age-related macular degeneration (5.2%), optic neuropathy (4.6%), corneal opacity (4.6%), and diabetic retinopathy (3.3%). Glaucoma (1.0%) and high myopia (0.39%) were minor ocular diseases among elderly Amis. The prevalence of diabetes was 15.4% and that of hypertension was 40.0%.ConclusionsTreatable diseases such as cataracts and pterygium were the most common ocular diseases in the Amis tribes. The relatively low incidence of glaucoma was likely due to the unique genetic background of this population.

Factors influencing the retrograde labeling of retinal ganglion cells with fluorogold in an animal optic nerve crush model.

Purpose: To investigate whether different crush durations or a different fluorogold (FG) injection timing can affect the efficiency of FG retrograde labeling of retinal ganglion cells (RGCs) in the optic nerve (ON) crush model. Methods: We performed the ON crush in rats with a clip at different durations or a jewel forceps to compare the effects of different crush methods with FG staining. RGC density was compared between the FG injection 1 week before the sacrifice of the animals (group A) and the injection before the crush experiment (group B). Double staining with CD11b and FG in the retinal sections was conducted to investigate the relationship between the overcounting of RGCs and microglia. Results: The FG-stained particles were significantly decreased at the distal part of the crush site compared to the proximal site of the ON with a crush duration of over 30 s or when crushed with the jewel forceps. Two weeks after ON crush, the RGC count was higher both in the central and mid-peripheral retinas in group B. The percentage of CD11b-stained cells among the FG-stained cells in the RGC layer of retinas in group B was higher than that of group A (34% in group B vs. 4% in group A, p = 0.0001). Overcounting of RGC density in group B was due to additional microglia with FG engulfing. Conclusions: Our results suggest that each laboratory should test its setting conditions to avoid factors influencing the RGC density measurement before conducting ON crush experiments.