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Dysmorphology and the orbital region: a practical clinical approach.

Dysmorphology is the field of medicine focusing on congenital developmental abnormalities due to exogenous teratogens, chromosomal anomalies, or to a defect in a single gene. Numerous syndromes have been reported and a growing number of genes or chromosomal anomalies are identified. The clinical observation of the face remains an essential part of the clinical evaluation of the patients. The orbital region, as other regions of the face, should be systematically evaluated. Orbital malformations can be isolated or part of a syndrome. In the diagnostic process, the orbital anomaly can be classified as a major feature (essential for the diagnosis), a moderate feature (important but not essential for the diagnosis), or a minor feature (contributing weakly to the diagnosis). The diagnoses of the main orbital anomalies in dysmorphology are reviewed and illustrated with relevant examples of syndromes that are presented as well as the usual landmarks used in clinical practice. Abnormal position of the eyes in syndromes such as hypertelorism, hypotelorism, primary or secondary telecanthus, asymmetry, and proptosis are discussed. Eyelid anomalies, such as cryptophthalmos, ablepharon, blepharophimosis, euryblepharon, or anomalies at the level of the eyelashes and eyebrows are described.

Craniofacial Abnormalities↗

Plaque radiation therapy for malignant melanoma of the iris and ciliary body.

PURPOSE: To report on plaque radiation therapy for malignant melanomas involving the iris and ciliary body. METHODS: Twenty-two eyes (22 patients) with anterior uveal melanomas were treated with (103)Pd ophthalmic plaque radiation therapy. Transillumination and ultrasonography were used to evaluate ciliary body involvement and posterior iris extension. Plaques were placed onto the cornea to treat the anterior tumor margins. The targeted-zone included the tumor and a 2 to 3 mm tumor-free margin. After plaque removal, patients were examined at 1 day, 7 days, 4 weeks, and then every 3 to 6 months thereafter. Systemic evaluations for possible metastatic disease were performed every 6 months. RESULTS: After plaque radiation therapy, the melanomas decreased in thickness (mean 47%) in all 22 eyes, and no secondary enucleation was performed. One patient died of metastatic melanoma 5 years after radiation therapy. Despite anterior plaque placement that covered portions of the cornea, no epiphora, eyelash loss, or visually significant corneal opacities were noted. Whereas 15 of 21 phakic eyes (71%) developed secondary cataract, no eyes developed ischemic or neovascular radiation maculopathy. Four eyes were noted to have glaucoma before treatment, and two developed it after irradiation. Twenty of 22 eyes (91%) were within 2 lines of their pretreatment visual acuity. After radiation, the mean +/- SD follow-up was 56 +/- 34.4 months (range, 9 to 117 months). CONCLUSIONS: Plaque radiotherapy of melanomas involving the iris and ciliary body resulted in excellent local control with preservation of vision. Although there was high incidence of secondary cataracts, (103)Pd plaque radiation therapy resulted in no visually significant corneal opacity or radiation retinopathy.

Brachytherapy↗

A six-month randomized clinical trial comparing the intraocular pressure-lowering efficacy of bimatoprost and latanoprost in patients with ocular hypertension or glaucoma.

PURPOSE: To compare the intraocular pressure (IOP)-lowering efficacy and safety of topical bimatoprost 0.03% with latanoprost 0.005%. DESIGN: Multicenter, randomized, investigator-masked clinical trial. METHODS: After washout of glaucoma medications, ocular hypertension or glaucoma patients were randomly assigned to once-daily bimatoprost 0.03% (n = 133) or latanoprost 0.005% (n = 136) for 6 months. The primary outcome measure was mean change from baseline IOP (8 AM, 12 PM, 4 PM). Secondary measures included mean IOP, ophthalmologic examination, adverse events, and the percentage of patients reaching specific target IOPs. RESULTS: Mean change from baseline IOP was significantly greater for bimatoprost patients than for latanoprost patients at all measurements on each study visit; 1.5 mm Hg greater at 8 AM (P <.001), 2.2 mm Hg greater at 12 PM (P <.001), and 1.2 mm Hg greater at 4 PM (P =.004) at month 6. At the end of the study, the percentage of patients achieving a > or = 20% IOP decrease was 69% to 82% with bimatoprost and 50% to 62% with latanoprost (P < or = .003). In addition, the distribution of patients achieving target pressures in each range (< or = 13 to < or = 15 mm Hg, >15 to < or = 18 mm Hg, and > 18 mm Hg) showed that bimatoprost produced lower target pressures compared with latanoprost at all times measured (P < or = .026). Few patients were discontinued for adverse events (6 on bimatoprost; 5 on latanoprost). On ophthalmologic examination, conjunctival hyperemia (P <.001) and eyelash growth (P =.064) were more common in bimatoprost patients. CONCLUSIONS: Bimatoprost is more effective than latanoprost in lowering IOP. Both drugs were well tolerated, with few discontinuations for adverse events.

Adult↗

Corneal perforation associated with argon laser photocoagulation for a retinal tear.

PURPOSE: To report a corneal perforation during argon laser photocoagulation around a retinal tear following pneumatic retinopexy. METHODS: The patient was examined and found to have a corneal perforation with pigment in the base of the wound. To help explain this phenomenon, we evaluated the ability of argon blue-green laser to create a corneal perforation in a cadaver eye. RESULTS: In a cadaver eye, we induced a corneal perforation with argon laser only when a pigmented substance was present on the corneal surface. CONCLUSIONS: We hypothesize that pigmented material such as an eyelash or mascara caught between the cornea and contact lens interface may have facilitated this rare complication. Clinicians should be wary of any pigmented substance on the surface of the cornea or ophthalmoscopic lens when performing argon laser photocoagulation.

Aged↗

Tarsal margin rotation with posterior lamella superadvancement for the management of cicatricial entropion of the upper eyelid.

PURPOSE: To report the efficacy of tarsal margin rotation with posterior lamella superadvancement in the management of cicatricial entropion of the upper eyelid. METHODS: In 15 consecutive patients, 22 eyelids with cicatricial entropion were managed with tarsal margin rotation and posterior lamella superadvancement. In a retrospective study, the technique and results were evaluated. RESULTS: In all 22 upper eyelids, the normal eyelashes rotated away from the surface of the eye. Mean follow-up was 12.9 +/- 12.4 months (range, 1 to 48 months). One eyelid developed buckling of the tarsus. Three eyelids needed electrolysis to treat isolated metaplastic cilia posterior to the normal lash line. CONCLUSIONS: Tarsal margin rotation with posterior lamella superadvancement appears to be effective in managing cicatricial entropion of the upper lid.

Adolescent↗

Serotonin 5-HT1A receptors might control the output of cortical glutamatergic neurons in rat cingulate cortex.

The present study was designed to investigate the distribution of serotonin 5-HT1A receptor protein (5-HT1A-immunoreactivity) and its localization within cortical pyramidal neurons of the rat cingulate cortex. This experimental direction was inspired by recent data showing the role of 5-HT1A receptors in the pathology of schizophrenia, and in the mechanism of action of novel antipsychotic drugs as well as by the importance of the cingulate cortex in regulation of cognitive functions. It was found that 5-HT1A-immunoreactivity was densely distributed in neuronal eyelash-like elements, and their size, shape and spatial orientation may suggest concentration of 5-HT1A-immunopositive material in the proximal fragments of axons of cortical neurons. Moreover, it was observed that these 5-HT1A-immunopositive fragments were present predominately on proximal fragments of axons of pyramidal neurons, which was evidenced by double labeling experiments using glutamate and non-phosphorylated neurofilament H as markers of the cortical pyramidal cells. The 5-HT1A receptor immunoreactivity was localized distally to the inhibitory GABAergic terminals of chandelier and basket cells surrounding the pyramidal cell bodies and occasionally surrounding short initial segment of axonal hillock of pyramidal neurons. These anatomical data indicate that 5-HT1A receptors might control the excitability and propagation of information transmitted by the pyramidal cells. Moreover, our results indicate that drugs operating via 5-HT1A receptors in the cingulate cortex might control from this level the release of glutamate in the subcortical structures. Finally, the 5-HT1A receptors present in the cingulate cortex, as demonstrated in the present study, may constitute an important target for drugs used to repair dysfunction of glutamate neurotransmission, which is observed for example in schizophrenia.

Animals↗

Use of midazolam as an induction agent: comparison with thiopentone.

A prospective, randomized, single-blind investigation was undertaken into the value of midazolam as an agent for the induction of anaesthesia. Sixty patients undergoing orthopaedic surgery of short duration were allocated randomly to receive either midazolam 0.2 mg kg-1 or thiopentone 3 mg kg-1. The induction time (measured as the time until loss of eyelash reflex) in the thiopentone group was significantly shorter than in the midazolam group. No differences were observed between the two drugs as regards time to onset of apnoea, or changes in heart rate and arterial pressure.

Adult↗

Intermittent reversal of complete ptosis associated with sphenoid wing meningiomas.

CASE REPORT: Ptosis secondary to dense oculomotor pareses generally improves over several months, but intermittent elevation of the eyelid has not been reported. The authors describe two patients who demonstrated intermittent involuntary monocular eyelid elevation in an eye with complete ptosis caused by partial resection of sphenoid wing meningioma. Both patients had complete ophthalmoplegia and decreased corneal sensation. The involved eye was ipsilateral to a meningioma that had been debulked 11 to 12 months previously. Although the lids were devoid of volitional movement, each patient could elevate the lid for 10 to 20 seconds by either tickling the eyelashes or rubbing the eyelids. The lids occasionally rose spontaneously and there was no clinical evidence of aberrant regeneration or cyclic spasm. COMMENTS: Although the mechanism of action of this involuntary eyelid elevation is unknown, it is possible that some process of aberrant regeneration activated by sensory stimuli is responsible.

Adult↗

Ophthalmic findings in GAPO syndrome.

BACKGROUND: The main manifestations of GAPO syndrome are growth retardation (G), alopecia (A), pseudoanodontia (P), and optic atrophy (O). CASES: This syndrome has been described in 21 patients from 16 different families. Four cases are from Turkey and have been presented by Sayli and Gül. The purpose of our study is to document the cases from Turkey and discuss the ophthalmological and neuro-ophthalmolgical findings of these and other reported GAPO cases. OBSERVATIONS: All patients in the literature and our 4 cases have severe growth retardation with delayed bone age in infancy, characteristic facial appearance (high and bossed forehead, midface hypoplasia), alopecia or severe hypotrichosis, and pseudoanodontia. Optic atrophy was present in 1 of our cases and in 5 previous cases. Glaucoma was present in 5 cases, including 2 of ours. Buphthalmia and keratopathy secondary to glaucoma were also observed. White eyelashes, seen only in our cases, may be a sign of "early senility." CONCLUSIONS: Optic atrophy is not a constant finding in GAPO syndrome. Glaucoma may accompany the ocular findings. This syndrome has been attributed to either ectodermal dysplasia or the accumulation of extracellular connective tissue matrix, due to an enzyme deficiency involved in its metabolism. Current studies show that an elastin defect and secondary changes in collagen may be important in the pathogenesis of the disease.

Abnormalities, Multiple↗

A new malformation syndrome of long palpebral fissures, large ears, depressed nasal tip, and skeletal anomalies associated with postnatal dwarfism and mental retardation.

Five unrelated patients with a previously unrecognized mental retardation malformation syndrome are presented. Clinical features common to them include moderate mental retardation, postnatal dwarfism, susceptibility to infection in infancy, and peculiar craniofacial dysmorphia characterized by long palpebral fissures, high-arched and abnormal eyebrows, heavy and long eyelashes, large ears, short nasal septum and/or depressed nasal tip, and cleft palate. Other anomalies are stubby fingers, deformed vertebra and other bone and joint anomalies, and abnormal dermatoglyphics. The absence of familial occurrence and of consanguinity suggests some environmental causation, but the possibility of an autosomal dominant or X-linked mode of inheritance remains. Based upon our five patients and other five of Niikawa et al, we propose this syndrome as a new disease entity.

Abnormalities, Multiple↗

Bimatoprost and travoprost: a review of recent studies of two new glaucoma drugs.

Bimatoprost (Lumigan [Allergan, Inc, Irvine CA]) and travoprost (Travatan [Alcon, Ft Worth, TX]) are two new intraocular pressure (IOP)-lowering drugs for use in patients with glaucoma and ocular hypertension. This review evaluates recent studies comparing these new drugs with timolol and with latanoprost. In each study, the statistical analyses support the conclusion that these agents were more effective than timolol and as effective as latanoprost in terms of their ability to reduce IOP. The side effect profiles for bimatoprost, latanoprost, and travoprost were similar, but with statistically higher occurrences of hyperemia and eyelash growth for bimatoprost or travoprost versus latanoprost or timolol.

Amides↗

Mathematical procedures in data recording and processing of pupillary fatigue waves.

Spontaneous pupillary behaviour in darkness provides information about a subject's level of vigilance. To establish infrared video pupillography (IVP) as a reliable and objective test in the detection and quantification of daytime sleepiness, the definition of numerical parameters is an important precondition characterising spontaneous pupil behaviour adequately for further statistical procedures. The correct measurement of the pupil size, even if the lid or eyelashes are occluding the pupil, is of particular concern when testing vigilance. In this case many edge points of the pupil are detected and a fitting procedure is described that fits these edge points to a circle and excludes outliers. The first step of data preparation consists of a mathematical artefact management consisting of blink detection and elimination, followed by interpolation. Second, a fast Fourier transformation is carried out for frequencies from 0.0 to 0.8 Hz for each time segment of 82 s. Results are given in absolute and relative power of each frequency band per time segment and mean values over the entire record of 11 min. Third, the changes of the mean pupillary diameter per data window against time are shown graphically. An additional parameter referring to the pupil's tendency to instability, the pupillary unrest index (PUI), is defined by cumulative changes in pupil size based on mean values of consecutive data sequences. These mathematical procedures provide a high level of quality in both data collection and evaluation of IVP as an objective test of vigilance. In a pilot study, the pupillary behaviour of two groups were measured. One group rated themselves as alert (ten men), the other group as sleepy (12 men). The power and PUI were compared using the Mann-Whitney U-test. Both parameters show significant differences between the two groups.

Data Interpretation, Statistical↗

Malignant melanoma of the eyelid and palpebral conjunctiva treated with iodine-125 brachytherapy.

OBJECTIVE: To evaluate the results on malignant melanomas of the eyelid and palpebral conjunctiva treated with iodine-125 (125I) brachytherapy with shielding of the eye. DESIGN: Noncomparative case series. PARTICIPANTS: Fourteen patients treated with 125I brachytherapy at an ocular oncology referral center from 1974 through 1996, all of whom had had previous debulking, incomplete resection, or recurrence after surgery. INTERVENTION: A stainless steel pericorneal ring eyeshield was attached to the extraocular muscles, over which a lid was fitted to protect the cornea without touching it. Iodine-125 seeds in polythene tubes were inserted into the eyelid and attached to the lid margin for a single plane implant. In five cases additional seeds were glued on to the shield as well for a volume implant. A median dose of 37 Gy (range, 17.3-67.6 Gy) was given over the course of 113 hours (range, 47-190 hours) to the outer surface of target volume. MAIN OUTCOME MEASURES: Local control is regarded as freedom from recurrence in those without measurable disease and complete clinical regression in those with measurable disease. Morbidity is assessed in terms of function and cosmesis. Survival is given from the time of the implant. RESULTS: There was local control in 13 patients maintained from 11 to 227 months (median, 39 months). There were two recurrences at 8 and 13 months in the first patient who received 17.3 Gy. Late complications consisted of mild eyelid telangiectasia, mild eyelid atrophy, and loss of eyelashes in most patients. Five patients, four of whom had upper eyelid tumors, experienced a dry eye, which was managed with tear supplements, and one of these patients developed a cataract. A corneal ulcer developed in one eye, which later perforated after treatment of a subsequent bulbar melanoma and was exenterated. Another eye was enucleated after treatment for a subsequent melanoma in the fornix. Cosmesis was acceptable to patient and doctor in the other 12 patients. Vision was maintained in seven patients, reduced in two, and not recorded in the remaining three patients. Three patients died of hematogenous metastases at 44, 62, and 79 months after implant, one of bronchial carcinoma at 46 months and one of an astrocytoma at 39 months. All patients were clear of local disease. The remainder survived for a median of 45 months (range, 18-227 months). CONCLUSIONS: Iodine-125 brachytherapy can be used as an alternative to wide excision or exenteration of these tumors. There was good local control, reasonable maintenance of vision, and good cosmesis.

Adult↗

Eyelid abnormalities in lamellar ichthyoses.

PURPOSE: To describe eyelid abnormalities in lamellar ichthyoses (LI). DESIGN: Retrospective observational case series. PARTICIPANTS: Eight patients with classic LI and two patients with congenital ichthyosiform erythroderma. METHODS: Results of eyelid and corneal examinations of 10 patients with LI were reviewed and analyzed with emphasis on the relationship between eyelid ectropion and corneal damage. RESULTS: All patients presented with cicatricial lagophthalmos. Of the eight patients with classic LI, five had ectropion of the four eyelids, one had only lower ectropion, and two had no degree of ectropion. Two patients with congenital ichthyosiform erythroderma had distinct eyelid abnormalities, including madarosis and eyelash retraction. Loss of vision caused by corneal damage was found in three patients with classic LI. Of these three patients, two did not have upper eyelid ectropion. CONCLUSIONS: Severe corneal damage can occur in LI even if there is no upper or lower eyelid ectropion.

Adolescent↗

Comparison of once- or twice-daily bimatoprost with twice-daily timolol in patients with elevated IOP : a 3-month clinical trial.

OBJECTIVE: To compare the safety, tolerability, and efficacy of bimatoprost 0.03% instilled once daily or twice daily with timolol 0.5% twice daily. DESIGN: Multicenter, 3-month, randomized, double-masked, interventional comparison trial. PARTICIPANTS: Patients diagnosed with ocular hypertension or glaucoma (n = 596). INTERVENTION: Patients received bimatoprost 0.03% ophthalmic solution once daily (8 PM, with vehicle control at 8 AM), bimatoprost 0.03% twice daily (8 AM; 8 PM), or timolol 0.5% twice daily (8 AM; 8 PM) in an uneven 2:2:1 randomization. Scheduled visits were at prestudy, baseline (day 0), weeks 2 and 6, and month 3. Intraocular pressure (IOP) was measured at 8 AM (predose), 10 AM, and 4 PM. MAIN OUTCOME MEASURES: The primary outcome measure was reduction in IOP in the eye with higher IOP at baseline. Secondary outcome measures included safety variables (adverse events, ophthalmoscopy, biomicroscopy, iris pigmentation, laser-flare meter, visual acuity, visual fields, heart rate, blood pressure, blood chemistry, hematology, and urinalysis). RESULTS: At month 3, the mean reduction in IOP from baseline at 8 AM was 9.16 mmHg (35.2%) with bimatoprost once daily, 7.78 mmHg (30.4%) with bimatoprost twice daily, and 6.74 mmHg (26.2%) with timolol twice daily. At all follow-up visits, mean IOP reductions were significantly greater in the bimatoprost once daily group than in the timolol group at each time point (8 AM, 10 AM, and 4 PM; P < 0.001). Twice-daily dosing of bimatoprost also provided significantly greater mean reductions in IOP than timolol at most time points but was not as effective as once-daily dosing. Bimatoprost was associated with significantly more hyperemia and eyelash growth than timolol, whereas timolol was associated with significantly more burning and stinging sensation in eyes. Overall, bimatoprost was well tolerated with few discontinuations because of adverse events. CONCLUSIONS: Bimatoprost 0.03% once daily was safe and statistically superior to timolol 0.5% twice daily in lowering IOP in patients with ocular hypertension or glaucoma. Bimatoprost given once daily consistently provided IOP reductions approximately 2 to 3 mmHg greater than those provided by timolol. Once-daily dosing of bimatoprost, 0.03%, demonstrated greater IOP-lowering effect and better ocular tolerability than twice-daily dosing.

Adult↗

Cryosurgery for malignancies of the eyelid.

The results of liquid nitrogen spray technique for 310 biopsy-proven eyelid malignancies are reviewed. The raw recurrence rate for basal cell carcinomas of the eyelids with a mean follow-up of almost three years is 4.2%, while the recurrence rate is 6% in 49 cases followed for five years. For all lid malignancies 10 mm or less in diameter, a 2.0% raw recurrence rate was obtained; however, in those lesions larger than 10 mm, this rose to 9.5%. With this form of therapy, basal cell carcinomas with infiltrative, nonelevated, indistinct borders had twice the recurrence rate than those tumors with elevated distinct borders. Twenty-one squamous cell carcinomas treated with cryosurgery with an average follow-up 21.6 months have yet to show a recurrence. Complications with cryosurgery include permanent loss of eyelashes and depigmentation lasting from six months to over six years. Depending on the extent and location of the tumor, eyelid defects occurred. To date, five plastic reconstructive procedures have been required for ectropion or lid defects; however, no lacrimal outflow surgery has as yet been required.

Adult↗

Laser microsurgery for superficial T1-T2 basal cell carcinoma of the eyelid margins.

BACKGROUND: Basal cell carcinoma (BCC), the most common malignancy of the eyelid margins, poses therapeutic problems. Surgery, radiation therapy, and cryotherapy are the currently accepted methods for the treatment of this affliction. To verify the technical and clinical effectiveness of the surgical laser method, a specific approach was developed by performing laser-combined procedures under microscopic control. METHODS: A series of 26 patients underwent carbon dioxide (CO2) laser microsurgical excision of 27 primary superficial BCCs of the eyelid margins. Eighteen tumors were T1 and 9 were T2. The lesions were located at the lid margins in 18 and at the canthus in 9 cases. The eyelash line was involved in all cases, whereas intermarginal space was involved in 17 cases, without extension to the conjunctival border. Six lesions were in the lacrimal region. Median linear extent of the lesion was 5 mm (range, 4-10 mm). Treatment was performed with the patient under local anesthesia in a Day Hospital regimen. The authors used the microscope-mounted CO2 laser as a scalpel to excise the tumor mass, thus obtaining the specimen for histologic evaluation. The authors treated the deep and lateral resection margins with laser vaporization and left the wound bed to heal by secondary intention. RESULTS: No significant complications were observed. As full-thickness eyelid resections were avoided, the authors noted conservation of lid function and cosmetic aspect in all patients. With a median follow-up of 73 months (range, 18-118), only one patient had tumor recurrence after 22 months. This tumor, located at the outer canthus, had a second microsurgical laser excision, and the patient is disease free 51 months after the last treatment. CONCLUSIONS: Laser microsurgery appears to be a safe and effective treatment method for primary superficial T1 and T2 BCC of the eyelid margins without conjunctival extension.

Adult↗