Multimodal imaging including spectral-domain optical coherence tomography and confocal near-infrared reflectance for characterization of lacquer cracks in highly myopic eyes.

PURPOSE: To compare multimodal imaging in detecting lacquer cracks in highly myopic eyes, and to correlate these findings with those of spectral-domain optical coherence tomography (SD-OCT). METHODS: An observational case series study. Patients with a refractive error worse than -8 diopters and lacquer cracks were recruited. The rates of detection of the lacquer cracks using multimodal imaging including near-infrared reflectance (NIR) imaging, fundus autofluorescence (FAF) imaging, and fluorescence angiography (FA) were compared. The characteristic findings of multimodal imaging were correlated with those of SD-OCT. RESULTS: NIR imaging was more sensitive (92.9%) in detecting lacquer cracks than either FAF (12.5%) or FA (67.9%). Lacquer cracks showed hyperreflectance on NIR, and they were consistently associated with a continuous retinal pigment epithelium-Bruch's membrane complex, thinner choroid, and acoustic shadows on SD-OCT. CONCLUSIONS: NIR imaging is superior to blue laser light (FAF and FA) imaging in detecting lacquer cracks. SD-OCT in combination with NIR located primary pathological lacquer cracks in the intact retinal pigment epithelium-Bruch's membrane complex as well as thinner choroid. These findings indicate that multimodal cSLO and SD-OCT imaging allow for detecting of lacquer cracks in highly myopic eyes.

Impaired skin wound healing in lumican-null mice.

BACKGROUND: Previous studies have demonstrated that the lack of lumican delayed corneal wound healing in lumican-null (Lum(-/-) ) mice. This defect is rescued by the addition of glycosylated lumican core protein to the injured corneas. OBJECTIVES: We examined the hypothesis that lumican is also required for the healing of cutaneous wounds using Lum(-/-) mice. METHODS: We demonstrated the basic thinner skin phenotypes in Lum(-/-) mice at different time points and the changes in arrangement of collagen fibres by transmission electron microscopy (TEM). A full skin thickness wound was generated by punch biopsy (6 mm diameter) in experimental Lum(-/-) and wild-type mice. The closure of injured skin was measured after various periods of time (3, 6, 12, 18 days). Specimens of injured and uninjured skin (serving as control) were then subjected to morphological examination with haematoxylin and eosin and Masson trichrome stains, and by TEM. Immunohistochemical staining with anti-CD68 antibody was used to assess the presence of macrophages in injured skin healing for various periods of time. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to elucidate the transforming growth factor (TGF)-ß1-induced myofibroblast phenotypic genes. RESULTS: Skin of adult Lum(-/-) mice (3 months and older) was much thinner (40% less) than that of age-matched wild-type mice. This phenomenon was aggravated in older mice. TEM revealed disoriented and irregular collagen fibrils in the dermis of Lum(-/-) mice. Delayed wound healing with an increase in inflammatory macrophages was compatible with the delayed response of the expression of TGF-ß1, type I collagen α1 and fibronectin at the mRNA level by semiquantitative RT-PCR in the Lum(-/-) mice. CONCLUSIONS: Our data demonstrate that lumican plays pivotal roles in skin collagen fibrillogenesis and wound healing.

Ectopic lacrimal gland cyst of the orbit.

Lacrimal duct cysts are not common. It is extremely rare when a lacrimal duct cyst and an ectopic lacrimal gland develop in the orbital cavity. A unique case of an ectopic lacrimal gland cyst of the orbit is presented. A 33-year-old man had a palpable mass above the inferior medial orbital rim for nearly two years. An ocular examination was normal except for a movable, firm mass found in the anterior nasal inferior orbit of the right eye. An echogram revealed a homogeneous, hypoechoic cystic mass. Computed tomography of the orbit showed a well-encapsulated lesion in the lower orbit of the right eye near the inferior rectus muscle, without bony erosion. A tense, thin-walled, clear fluid-filled cyst measuring 15 x 12 x 13 mm in size was completely enucleated without rupture by anterior orbitotomy. Pathologic examination disclosed a small nest of normal gland tissue surrounded by a cystic lesion lined with two layers of lacrimal duct epithelium cells. No recurrent signs were noticed during a 12-month period of follow-up.

Mapping the melatonin receptor. 6. Melatonin agonists and antagonists derived from 6H-isoindolo[2,1-a]indoles, 5,6-dihydroindolo[2,1-a]isoquinolines, and 6,7-dihydro-5H-benzo[c]azepino[2,1-a]indoles.

6H-Isoindolo[2,1-a]indoles (5, 7, 10, 13), 5,6-dihydroindolo[2, 1-a]isoquinolines (20, 21), and 6,7-dihydro-5H-benzo[c]azepino[2, 1-a]indoles (23, 25, 27, 30) have been prepared as melatonin analogues to investigate the nature of the binding site of the melatonin receptor. The affinity of analogues was determined in a radioligand binding assay using cloned human mt(1) and MT(2) receptor subtypes expressed in NIH 3T3 cells. Agonist and antagonist potency was measured using the pigment aggregation response of a clonal line of Xenopus laevis melanophores. The 2-methoxyisoindolo[2, 1-a]indoles (7a-d) showed much higher binding affinities than the parent isoindoles (5a-e), and whereas 7a-c were agonists in the functional assay, 7d and 5a-e were antagonists. The 2-ethoxyisoindolo[2,1-a]indoles (10a-d) showed reduced binding affinities compared to their methoxy analogues, while the 5-chloro derivative 13 showed a considerable reduction in binding affinity and potency compared to 7a. The 10-methoxy-5,6-dihydroindolo[2, 1-a]isoquinolines (21a-c) had higher binding affinities than the corresponding parent indoloisoquinolines (20a-c) in the human receptor subtypes, and the parent compounds were antagonists whereas the 10-methoxy derivatives were agonists in the functional assay. The N-cyclobutanecarbonyl derivatives of both the parent (20d) and 10-methoxyl (21d) series had similar binding affinities and were both antagonists with similar potencies. The 11-methoxy-6, 7-5H-benzo[c]azepino[2,1-a]indoles (25a-d) had higher binding affinities than the corresponding parent compounds (23a-d) at the MT(2) receptor but similar affinities at the mt(1) site; all of the compounds were antagonists in the functional assay. Changing 11-methoxy for 11-ethoxy decreased the binding affinity slightly, and this was more evident at the MT(2) receptor. All of the derivatives investigated had either the same or a greater affinity for the human MT(2) receptor compared to the mt(1) receptor (range 1:1-1:132). This suggests that the mt(1) and MT(2) receptor pockets differ in their ability to accommodate alkyl groups in the indole nitrogen region of the melatonin molecule. Two compounds (7c and 25c) were tested in functional assays on recombinant mt(1) and MT(2) melatonin receptors. Compound 7c is a potent agonist with some selectivity (44-fold) for the MT(2) receptor, while 25c is an MT(2)-preferring antagonist. Increasing the carbon chain length between N-1 of indole and the 2-phenyl group from n = 1 through n = 3 leads to a fairly regular decrease in the binding affinity, but, remarkably, when n = 3, it converts the methoxy compounds from melatonin agonists to antagonists. The Xenopus melatonin receptor thus cannot accommodate an N-n-alkyl chain attached to a 2-phenyl substituent with n > 2 in the required orientation to induce or stabilize the active receptor conformation.

Delayed-onset of Pseudomonas infection in a hydroxyapatite orbital implant: a case report.

Hydroxyapatite (HA) orbital implant, a multiple porous coralloid-like material, is frequently used in orbital reconstruction after enucleation or evisceration surgery. HA implants contain multiple interconnected pores in which rich fibrovascular tissue ingrowth could theoretically help to resist infection. Infection of hydroxyapatite implants are rare. Most HA implant infections occur before complete vascularization. We present this first case in Taiwan of delayed-onset Pseudomonas infection five years after receiving the HA implant. There was not much improvement after intensive medications, so removal of the implant was finally performed. The pathology study disclosed diffuse inflammatory cell infiltration in the whole implant with a necrotic central core. Rich fibrovascular ingrowth was also noted. Once a porous HA implant is infected, the infection is difficult to control and becomes more severe due to the dead space of the interconnected pores. Removal of the implant seems to be the only successful treatment modality.

Design of subtype selective melatonin receptor agonists and antagonists.

Studies of the physiological actions of melatonin have been hindered by the lack of specific, potent and subtype selective agonists and antagonists. In the present study, we describe the utility of a melanophore cell line from Xenopus laevis for exploring structure-activity relationships among novel melatonin analogues and report a novel MT2-selective agonist (IIK7) and MT2-selective receptor antagonist (K185). IIK7 is a potent melatonin receptor agonist in the melanophore model, and in NIH3T3 cells expressing human mt1 and MT2 receptor subtypes. In radioligand binding experiments IIK7 is 90-fold selective for the MT2 subtype. K185 is devoid of agonist activity, but acts as a competitive melatonin antagonist in melanophores. A low concentration (10(-9) M) antagonizes melatonin inhibition of forskolin stimulation of cyclic AMP in NIH3T3 cells expressing human MT2 receptors, but has no effect in cells expressing mt1 receptors. In binding assays, K185 is 140-fold selective for the MT2 subtype.

Solar retinopathy: a case report.

Sun-gazing is the main cause of solar retinopathy. A 20-year-old inebriated man lying in a park gazed at the sun for approximately three hours at noon. Forty-eight hours after sun-gazing, the patient experienced the symptoms of blurred vision, erythropsia, and central scotoma in the left eye. Visual acuity decreased from 6/6 to 6/60 in the left eye and fundi examinations showed a round, yellowish-white discoid lesion on the left fovea and a smaller one on the right fovea. Fluorescein angiography showed early dye leakage in the fovea of the left eye, that increased gradually in size and became fuzzy at the foveal border in the late phase. A small, central scotoma of the left eye was also found in the visual field test. One month later, the lesion in the fovea of the left eye became smaller and was surrounded by a coarse pigmented halo. Fluorescein angiography showed a window defect in the retinal pigment epithelium. Visual field testing disclosed that the central scotoma persisted, but became smaller. Six months after sun-gazing, a lamellar hole in the fovea of the left eye was detected by optical coherence tomography. The visual acuity was 6/6 in the right eye and 6/60 in the left eye, and was unchanged at the end of the six-month follow-up period.