Reduced amplitude and delayed latency in foveal response of multifocal electroretinogram in early age related macular degeneration.

AIM: To explore the use of multifocal electroretinograms (MERG) in detecting early changes in age related macular degeneration (AMD). METHOD: 15 pre-AMD or early AMD eyes showing retinal drusen or irregular fundus pigmentation with window defects by fluorescein angiography (FA) and mildly decreased visual acuity were examined and compared with their asymptomatic fellow eyes. 20 age matched normal eyes were included as controls. MERG was recorded by a Veris system (version 3.0) using a 103 hexagon stimulus and 218 second total recording time per eye. The first order kernel was used to calculate amplitudes and latencies in three configurations: the nasal and the temporal areas, the superior and the inferior areas, and six concentric rings centred on the fovea. RESULTS: There were no significant differences in the amplitudes and the latencies between the different regions (nasal versus temporal and superior versus inferior) of the retina as well as between the different groups of eyes (normal, pre-AMD or early AMD, and the asymptomatic fellow eyes) in each region. Using the concentric configuration, the foveal amplitude of pre-AMD or early AMD eyes was significantly suppressed when compared with the age matched control group and their average latency was longer in the fovea than in outer rings and significantly prolonged when compared with the normal control group. Similar changes in amplitude and latency were also observed in the asymptomatic fellow eyes. CONCLUSION: Significant abnormality in the foveal amplitude and the foveal latency of MERG could be detected in pre-AMD or early AMD eyes as well as their asymptomatic contralateral eyes, suggesting MERG as a sensitive tool in detecting early foveal abnormalities in AMD.

International Federation of Ophthalmological Societies statutes and regulations.

PURPOSE: To provide an understanding of the structure, role, and responsibility of the International Federation of Ophthalmological Societies, the International Council of Ophthalmology, and the International Congress of Ophthalmology. These established entities have recently codified their statutes and regulations and registered them in Zurich, Switzerland. METHODS: The International Council of Ophthalmology, which serves as the executive body of the International Federation of Ophthalmological Societies, used historical operating documents to prepare the statutes and regulations, which were reviewed and adopted by the International Federation of Ophthalmological Societies at the 28th International Congress of Ophthalmology in Amsterdam on June 23, 1998. RESULTS: The statutes and regulations of the International Federation of Ophthalmological Societies, the International Council of Ophthalmology, and the International Congress of Ophthalmology are available to supranational ophthalmological organizations, national ophthalmological societies, other ophthalmological organizations, and individual ophthalmologists. CONCLUSIONS: The statutes and regulations of the International Federation of Ophthalmological Societies, the International Council of Ophthalmology, and the International Congress of Ophthalmology provide a basis for an organizational structure in international ophthalmology. The International Congress of Ophthalmology, first held in 1857, is the longest continuing international meeting in medicine. The International Council of Ophthalmology was established in 1927, and the International Federation of Ophthalmological Societies was formed in 1933. These organizations coordinate the International Congress of Ophthalmology, which convenes with the International Federation of Ophthalmological Societies every 4 years. The International Council, as the executive body, meets annually. The International Council of Ophthalmology has for decades worked to coordinate and facilitate interchange, education, and standards in international ophthalmology. Currently, the International Council of Ophthalmology, working with other international organizations, is creating an international ophthalmology strategic plan, which includes focus on ophthalmic training, continuing education, advocacy for the preservation and restoration of vision, clinical guidelines, and research.

c-Fos protein in photoreceptor cell death after photic injury in rats.

PURPOSE: To examine the involvement of c-Fos protein in light-induced photoreceptor cell death in rats. METHODS: Thirty-two Lewis albino rats were exposed to green fluorescent light (480-520 nm) of 300 to 320 foot-candles (3228-3443.2 lux) for 3 hours, allowed to recover in the dark, and euthanatized at 0, 1, 3, 6, 12, 24, or 96 hours after light exposure. c-Fos was detected immunohistochemically and nicked DNA by in situ TdT-dUTP terminal nick-end labeling (TUNEL). Double labeling of c-Fos and DNA nicks was also performed. RESULTS: There was a time-dependent change in the number of c-Fos-positive photoreceptor nuclei after light injury, which paralleled the change in the number of TUNEL-positive nuclei. The temporal and spatial appearance of these nuclei also matched the appearance of pyknotic nuclei of the outer nuclear layer. Double-labeling study revealed that some c-Fos-positive nuclei were also TUNEL-positive nuclei. CONCLUSIONS: There was an acute accumulation of c-Fos protein in photoreceptors associated with cell death. This study further supports other studies showing that c-Fos is linked to apoptotic photoreceptor cell death.

Changes of cytochemical markers in the conjunctival and corneal epithelium after corneal debridement.

1. The aim of this study was to determine the epithelial changes of the conjunctiva and cornea up to 7 days after corneal debridement and the changes highlighted included (1) proliferation, (2) production of growth factor, (3) changes in calcium binding protein marker, (4) production of cytokine, and (5) maturity of the regeneration corneal epithelium. 2. The cytochemical changes of the corneal and conjunctival epithelia of rabbit were analyzed up to 7 days after debridement. 3. An increase in proliferating cell nuclear antigen (PCNA) was observed in the limbal epithelia 12 hr after lesion and reached a peak by 48 hr. 4. Some proliferating limbal cells also contained epidermal growth factor (EGF) beginning 24 hr after injury. The early limbal cell proliferation and the EGF production and their persistence until 7 days after lesion were likely involved with the process of regeneration. 5. Other positive markers appeared after lesion included tumor necrosis factor (TNFalpha) and calcium binding proteins S100A and S100B, which appeared mainly within the first 48 hr after lesion and then started to decline. The short appearance and the relatively small quantity of TNFalpha indicated that this cytokine was probably not very important in the repair process and its appearance might be related to the injury induced. The presence of S100A and S100B could be associated with both cell death after injury and the proliferation of new epithelium. 6. The cornea epithelium was still immature 7 days after lesion in that it still contained cytokeratin. 7. In conclusion, the critical hours of peak conjunctival and corneal changes after corneal debridement were in the first 2 days.

The identification of dipalmityl zeaxanthin as the major carotenoid in Gou Qi Zi by high pressure liquid chromatography and mass spectrometry.

The carotenoid in Gou Qi Zi was extracted by hexane, followed by repeated chromatography on a silica column. The major carotenoid recovered from the chromatographic step was subjected to hydrolysis in potassium hydroxide (KOH). The hydrolytic products were separated on a silica column followed by analysis for their molecular sizes by a Micromass Platform LCZ. The retention time of the carotenoid in Gou Qi Zi is 2.3 min. Upon hydrolysis, new carotenoid peaks appeared. The molecular ions detected by APCI- of the carotenoid at 2.3, 6.8 and 28 min are 1044, 806 and 568, respectively. The molecular sizes matched to that of dipalmityl zeaxanthin, monopalmityl zeaxanthin and zeaxanthin, respectively. The monopalmityl zeaxanthin peak appeared first and faded away as the free zeaxanthin peak reached the maximal size.

Mucoepidermoid carcinoma of the eyelid skin.

PURPOSE: Mucoepidermoid carcinoma involving the eye or its adnexa generally arises from the conjunctiva. We describe a nodular lesion of the lower eyelid skin with histologic features consistent with low-grade mucoepidermoid carcinoma. METHOD: Case report. RESULTS: By histology, the tumor demonstrated areas of squamous cell carcinoma and scattered islands of mucin-secreting cells. Histochemistry showed hyaluronidase-resistant mucin and intense immunoreactivity with an antibody against carcinoembryonic antigen suggesting that the tumor originated from acrosyringeal structures. CONCLUSIONS: To our knowledge, this is the first report of a mucoepidermoid carcinoma arising from sweat glands in the eyelid skin.

N-methyl-D-aspartate (NMDA)--induced apoptosis in rat retina.

PURPOSE: The involvement of apoptosis in N-methyl-D-aspartate (NMDA)-induced excitotoxicity in adult rat retinas was examined. METHODS: Excitotoxic loss of inner retinal elements was induced by intravitreal injections of various concentrations of neutralized NMDA in adult albino Lewis rats. Tissue responses were quantified by measuring the inner retinal thickness (IRT) in plastic sections of the retinas and cell counts in the retinal ganglion cell layer in flatmount preparations of the whole retinas. Internucleosomal DNA fragmentation, a hallmark of apoptosis, was assayed with agarose DNA gel electrophoresis. The in situ TdT-mediated biotin-dUTP nick end labeling (TUNEL) method was used to locate nicked DNA in paraffin sections of the retinas. Ultrastructural changes of the degenerating cells were examined by electron microscopy. The efficacy of Ac-Tyr-Val-Ala-Asp-CMK (YVAD-CMK), a peptidyl caspase inhibitor, and 3-aminobenzamide (ABA), an inhibitor of poly(ADP-ribose) polymerase (PARP), in ameliorating the loss of inner retinal elements was evaluated using morphometry to examine the apoptotic pathways. RESULTS: Intravitreal injection of NMDA induced a dose-dependent loss of inner retinal elements as evidenced by the measurements of IRT and RGCCs. There were time- and dose-related appearances of internucleosomal fragmentation of retinal DNA and a time-related appearance of TUNEL-positive nuclei in the inner retinas after intravitreal NMDA injection. Ultrastructural features consistent with classic apoptotic changes were noted in degenerating cells in the retinal ganglion cell layer and the inner nuclear layer. Control retinas given vehicle, N-methyl-L-aspartate (the L-isomer of NMDA), or NMDA plus MK-801, a specific antagonist, did not show these changes. Simultaneous administration of NMDA and YVAD-CMK or ABA abolished or attenuated the loss of RGCCs in the posterior retinas. CONCLUSIONS: NMDA-induced excitotoxicity involved apoptosis and caspases and PARP may play important roles in the pathways.

Apoptosis and caspases after ischemia-reperfusion injury in rat retina.

PURPOSE: Extensive cell loss in the retinal ganglion cell layer (RGCL) and the inner nuclear layer (INL) was noted in a rat model of retinal ischemia-reperfusion injury by transient elevated intraocular pressure (IOP). The possible involvement of apoptosis and caspases was examined in this model of neuronal loss. METHODS: Transient elevated IOP was induced in albino Lewis rats through the insertion of a needle into the anterior chamber connected to a saline column. Elevated IOP at 110 mm Hg was maintained for 60 minutes. Groups of animals were euthanatized at various times after reperfusion, and their retinas were evaluated by morphology, agarose gel electrophoresis of DNA, in situ terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling (TUNEL), immunohistochemistry of caspases II (ICH1) and III (CPP32), and morphometry. YVAD.CMK, a tetrapeptide inhibitor of caspases, was used to examine the involvement of caspases. RESULTS: A marked ladder pattern in retinal DNA gel analysis, typical of internucleosomal DNA fragmentation and characteristic of apoptosis, was present 12 and 18 hours after reperfusion. Labeling of nuclei in the RGCL and the inner nuclear layer (INL) by TUNEL was noted between 8 and 18 hours after reperfusion. Histologic and ultrastructural features typical of apoptosis were also observed in the inner retina after ischemia. YVAD.CMK administered during the ischemic period inhibited apoptotic fragmentation of retinal DNA and ameliorated the tissue damage. When administered intravitreally 0, 2, or 4 hours after reperfusion, YVAD.CMK was also effective in preserving the inner retina but had no significant effect when administered 6 or 8 hours after reperfusion. The inner retina showed transient elevated immunoreactivity of caspases II and III 4 and 8 hours after reperfusion. CONCLUSIONS: Retinal ischemia-reperfusion after transient elevated IOP induced apoptosis of cells in the retinal ganglion cell layer and the INL. Caspases may have a pivotal role in the early events of the apoptotic pathway(s). Rescue by using anti-apoptotic agents after ischemia-reperfusion is feasible.

Ocular complications of pediatric bone marrow transplantation.

OBJECTIVE: To investigate the ocular complications in pediatric bone marrow transplantation (BMT) patients. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 29 pediatric BMT patients were studied. TESTING: Comprehensive ophthalmic check-up, including best-corrected visual acuity, intraocular pressure (IOP), Schirmer's test, tear breakup time, and slit-lamp and fundus examinations, was performed. MAIN OUTCOME MEASURES: Tear film instability and its related complications, IOP, cataract, and fundus lesions were measured. RESULTS: The mean age of patients was 9.1 years (range, 1.5-15 years). The mean post-BMT duration was 20.2 months (range, 3-54 months). Fifteen patients (51.7%) had tear abnormalities. Subconjunctival fibrosis was detected in two patients (6.9%). Dry and scaly skin of the eyelids was seen in one patient (3.4%). Lens opacities were found in 2 (33.3%) of 6 irradiated patients and 2 (8.7%) of 23 nonirradiated patients. Two patients (6.9%) had fundus changes, one with unilateral epiretinal membrane and the other with bilateral multiple discrete chorioretinal hypopigmented lesions in the middle to peripheral part of the retina. The overall complication rates for the anterior and posterior segments were 75.8% and 6.9%, respectively. CONCLUSION: Ocular manifestations of BMT in children are not uncommon. The most common anterior segment problem is tear dysfunction. Posterior segment complications are less common but do exist. High rate of cataract formation is reported, and this probably is the most important long-term "amblyogenic" problem in these immature eyes. Awareness and management of these problems with routine eye examination and early intervention are recommended.

The occurrence of retinol and carotenoids in human subretinal fluid.

PURPOSE: To investigate if retinol and carotenoids are present in the subretinal space following rhegmatogenous retinal detachment. METHODS: Blood and subretinal fluid were collected from patients at the time of surgical repair of retinal detachment. After removal of cellular contents in a specimen by centrifugation, the supernatant fraction was analyzed by liquid chromatography using a silica column eluted by 16% dioxane in hexane. Retinol and carotenoids were identified in the chromatograms based on their retention time and absorption spectrum. RESULTS: The retinol concentrations (mean+/-SD) in the serum and subretinal fluid were 305+/-144 and 166+/-96 ng/ml respectively. The 450 nm chromatogram had 7 peaks with the characteristic absorption spectrum of carotenoids. Peak 1 and 7 coincided with the retention time of beta-carotene (1.8 min) and lutein (10.8 min) respectively. The concentrations of beta-carotene and lutein in serum were 161+/-63 and 142+/-98 ng/ml respectively. There was very little beta-carotene in subretinal fluid (4.7+/-2.4 ng/ml). Lutein was the major carotenoid peak in subretinal fluid (41.4+/-14.1 ng/ml). The minor carotenoid peaks of serum were not observed in subretinal fluid. CONCLUSION: There is a substantial amount of retinol and lutein in subretinal fluid. The high proportion of lutein and very low amount of beta-carotene in the subretinal fluid support the occurrence of a highly selection transport mechanism of lutein from the blood to the retina.

Benign fibrous histiocytoma of the choroid.

Benign fibrous histiocytoma (BFH) is a common soft tissue tumour. However, its occurrence in the orbit was not well recognised in the past. It is only in recent years that this condition has become more frequently diagnosed. Now, it is believed to be the commonest mesenchymal tumour of the orbit in adults. Its occurrence in the uveal tract is, however, exceedingly rare. Only one case of presumed fibrous histiocytoma of the choroid has been reported in the literature. We report herein a case of BFH of the choroid in the left eye of a Chinese woman. The patient presented with a huge but asymptomatic raised choroidal mass. Results of choroidal biopsy showed no sign of malignancy but definitive diagnosis could not be made. Enucleation was finally performed. The diagnosis was made on detailed evaluation of the results of the immunohistochemical staining and the ultrastructural findings. The patient remained well at the latest follow-up, which was 33 months after enucleation. Although BFH of the choroid is vary rare, its benign nature and the availability of choroidal biopsy for tissue diagnosis make it important to include this as one of the differential diagnoses for amelanotic choroidal mass.

Intraoperative mitomycin C to prevent recurrence of pterygium after excision: a 30-month follow-up study.

OBJECTIVE: The purpose of the study was to examine the efficacy of intraoperative mitomycin C (MMC) in preventing recurrence of pterygium after excision and the postoperative complications encountered. DESIGN: The study design was a prospective, randomized, clinical trial. PARTICIPANTS: A total of 180 primary and recurrent pterygia were recruited for the study. They were randomized into five groups: A, control with no MMC; B, 0.02% MMC for 5 minutes; C, 0.04% MMC for 5 minutes; D, 0.02% MMC for 3 minutes; and E, 0.04% MMC for 3 minutes. INTERVENTION: All patients received pterygium excision with or without the above four modes of intraoperative MMC application. MAIN OUTCOME MEASURES: Recurrence of pterygium and postoperative complications such as superficial scleral melting were measured. RESULTS: At a mean follow-up of 30 (groups A-C) and 20 months (groups D and E), the respective recurrence rates in groups A through E were 75%, 8.3%, 8.6%, 42.9%, and 22.9%. There were two cases of postoperative superficial scleral melting in group C. Otherwise, no major postoperative complications were encountered. CONCLUSIONS: The midterm results of a single intraoperative application of MMC at the concentration of 0.02% for 5 minutes are encouraging. Its application as an adjunctive therapy for the surgical treatment of pterygium appeared to be safe and effective. However, because of the possibility of serious late complications, the authors suggest that this procedure be reserved for patients who have high probability of recurrence after excision of pterygium.

Iron-induced apoptosis in the photoreceptor cells of rats.

PURPOSE: To determine whether apoptosis is involved in retinal degeneration induced by intravitreal implantation of 5 iron particles in rat eyes. METHODS: Autoclaved iron particles were implanted in the vitreous cavities of the experimental eyes. Glass chips were implanted in the control eyes. The experimental eyes were enucleated at various time intervals from days 1 to 15. Retinal degeneration was examined using the TdT-mediated, dUTP-biotin nick-end labeling (TUNEL) method. Electrophoresis on agarose gel was used to detect internucleosomal DNA fragmentation. RESULTS: TUNEL-positive nuclei were observed only in the outer nuclear layer beginning on day 2. The nuclei spread throughout the outer nuclear layer by the end of day 3. No TUNEL-positive nuclei were observed in other layers throughout the experimental period. Analysis of DNA, extracted from the retinas by electrophoresis on agarose gel, revealed a typical ladder pattern of internucleosomal DNA cleavage in the experimental eyes. CONCLUSIONS: Apoptosis occurred during photoreceptor cell death at the early phase of iron-induced retinopathy in these rats. Like photic injury, iron-induced apoptosis was limited to the outer nuclear layer.

Ocular-hypertensive response to topical steroids in children.

OBJECTIVE: The purpose of the study is to investigate the rate and degree of ocular-hypertensive response to topical steroids in Chinese children. DESIGN: The study design was an institutional, randomized, clinical trial. PARTICIPANTS: A total of 19 consecutive patients were studied. INTERVENTION: Topical steroids were administered to Chinese children younger than 10 years of age who underwent bilateral strabismus surgery. One eye was randomized to receive topical 0.1% dexamethasone (DMS), whereas the fellow eye received 0.1% fluorometholone (FML) six times per day for up to 4 weeks. Intraocular pressure (IOP) was measured on the day before operation and at postoperative days 1, 3, 6, 10, 13, and 27, then every 2 weeks thereafter until the IOP fell to preoperative levels. Topical steroids would be stopped if IOP was 30.00 mmHg or greater. MAIN OUTCOME MEASURES: Peak IOP and maximal change of IOP from baseline were measured and categorized into low, intermediate, and high levels. Time to peak IOP also was studied. RESULTS: A total of 16 patients were included. The peak IOP for DMS-treated eyes was 30.66 +/- 8.35 mmHg (range, 13.00-48.00 mmHg), whereas that in FML-treated eyes was significantly lower at 20.66 +/- 6.03 mmHg (range, 11.30-36.30 mmHg) (P = 0.001). The maximal change in IOP ranged from -2.60 to +31.00 mmHg in DMS-treated eyes (mean, 15.48 +/- 8.71 mmHg), almost double that of FML-treated eyes (range, +1.00 to +17.00 mmHg; mean, 5.83 +/- 4.96 mmHg) (P = 0.001). When the ocular-hypertensive responses of both DMS and FML groups were categorized into three levels of severity, significant differences were found between the two treatment groups (P = 0.001). In the DMS group, nine patients (56.25%) were high responders and six patients (37.5%) were intermediate responders. In the FML group, only one patient (6.25%) was a high responder. CONCLUSIONS: The ocular-hypertensive response to topical DMS in children occurs more frequently, more severely, and more rapidly than that reported in adults. A total of 56% of the studied children, all younger than 10 years of age, were high responders to topical DMS. Of these, 89% attained their peak IOP within 8 days. Its use in children should best be avoided if possible. It would be desirable to monitor the IOP when it is being used. Conversely, FML produced a much less ocular-hypertensive effect and therefore poses an acceptable risk of clinically significant pressure elevation.

Unscheduled DNA replication precedes apoptosis of photoreceptors expressing SV40 T antigen.

Expression of simian virus 40 T antigen (Tag) in the rod photoreceptors of transgenic mice leads to cell death that is completed by the end of the third week of postnatal development. To understand the mechanistic link between Tag expression and the death of the expressing photoreceptors, cell cycle activity was followed in a transgenic mouse family that expresses Tag directed by the mouse opsin promoter. Tag-expressing photoreceptors also expressed rhodopsin suggesting that these cells were differentiated. The presence of Tag in the photoreceptors induced the expression of both proliferating cell nuclear antigen (PCNA) and thymidine kinase (TK). The abnormally high levels of PCNA and TK continued until the complete disappearance of the cells expressing Tag. Photoreceptor cell death was also associated with continued DNA synthesis that ceased shortly after postnatal day 16. The specific loss of the rod photoreceptors that re-entered the cell cycle accounted entirely for the loss of photoreceptors from the outer nuclear layer. The antiproliferative nature of the mature retina is directly involved in the apoptotic death of photoreceptors expressing Tag.