Computerised 3D evaluation of the functional eyelid deficit in facial palsy.

Facial palsy is often characterised by a severe dysfunction of the eyelids, leading to corneal ulceration and even blindness. A precise evaluation of the exposed ocular surface is very important in order to estimate the risks of these ocular symptoms. In the literature, most authors use a comparison between the heights of lagophthalmus and corneal exposure in the pre- and postoperative situations to evaluate the surgical correction of the eyelids in facial paralysis. The heights are not representative of the real exposed surfaces. We propose another method to evaluate these surfaces, using a computer-assisted design (CAD) software analysing standardised photographs and giving a precise assessment of the surface of the eye not covered by the eyelids. The exposed surface is more representative of the risks of ocular symptoms than the height. Our goal in this study was to improve the quality of the measurements, which allows to get a better estimation of the clinical situation and provides a tool that permits comparison of results between different surgical approaches.

[Management of eyelid tumors: general considerations]. / Prise en charge des tumeurs palpébrales : considérations générales.

Despite the fact that the majority of eyelid tumors are benign, proper management in daily practice requires detection of the malignant ones. Several clinical criteria are usually proposed to support or reject a hypothesis of malignancy; however, most are of limited reliability. In any case of doubt, outpatient biopsy is recommended, so as to establish the correct diagnosis and formulate the most appropriate treatment plan. In all facial malignancies, the first (and absolutely mandatory) consideration is control of the cancer. Then, restoration of eyelid function can be addressed, in the following order: protection of the globe by complete dynamic eyelid closure and opening, visual function (and prevention of possible deprivation amblyopia) by insuring a clear visual axis, correction of the tear film, efficient lachrymal drainage, and only then the role of the eyelids in facial expression and esthetics. For most malignant eyelid tumors, the best assurance of complete excision is obtained by extemporaneous examination of the resection margins by frozen section (by Mohs' micrographic surgery techniques, or a variation thereof). Currently, advancement and transposition flaps, possibly in combination with tarso-conjunctival or skin grafts, are the most utilised techniques. Despite the lack of histological verification, new treatment modalities, including topical chemotherapy, photodynamic therapy and cryotherapy, may provide interesting treatment options, particularly in collaboration with the dermatologist.

[The pathology of ocular syndromes caused by toxicity]. / La pathologie des annexes oculaires d'origine toxique.

Ocular adnexa represent a complex system of delicate organs and functions which are the target of varied side effects. Most involve more than one component at a time, however landmark signs and symptoms can be outlined. Dry eye leads the list. The aqueous production of the tear film can be decreased by certain psychotherapeutic agents (especially the older ones), while the phospholipidic component, produced by the Meibomian glands, can be markedly affected by retinoids. On the other hand, cytostatic drugs like Docetaxel (and 5-FU at a lesser degree) frequently induce canalicular stenosis, resulting in epiphora. Amongst a long list of substances, diphosphonates used in the treatment of osteoporosis and phosphodiesterase-5 inhibitors used in erection deficiencies induce conjunctival irritation, either directly or by contiguity. Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis represent the most severe toxic insult to the mucosae. A recent chemotherapeutic agent, Imatinib, induces fluctuant palpebral edema in a majority of patients. Despite being applied topically, prostaglandin analogs exert a profound effect onto the cellular physiology of the eyelash and the ocular and palpebral melanocyte. Indirectly, immunosuppressive agents used in graft rejection control have been associated with the emergence of secondary neoplasia, mainly lymphoma, of which the orbit is a rare but possible location. Chronic administration of steroid drugs leads to hypertrophy of the orbital fat and proptosis.

Biclonal low grade B-cell lymphoma confirmed by both flow cytometry and karyotypic analysis, in spite of a normal kappa/lambda Ig light chain ratio.

Composite low grade lymphoma with two subpopulations in a same site is uncommon. We herewith report the case of an 80-year-old woman who presented with isolated bilateral dacryoadenomegaly. Pathological examination of an incisional biopsy of her right lacrimal gland was consistent with a marginal zone lymphoma. Flow cytometry immunophenotyping showed two distinct clonal B-cell populations expressing sIg D lambda or sIg M kappa restriction in the lacrimal gland, blood, and bone marrow. Both B-cells populations were sorted from peripheral blood for molecular biology investigations and comparison with molecular data performed on tumor and bone marrow cells. IgH PCR performed on purified blood populations disclosed two monoclonal peaks: 98 bp-sized peak in the sIg M kappa and a 107 bp in the sIg D lambda clones, respectively. The lacrimal gland tumor expressed mainly sIg M kappa population, and showed a major 98 bp-sized peak coexisting with a very minor 107 bp peak. Cytogenetic studies showed a 46, XX,del (7) (q22q32) karyotype. Bone marrow examination at diagnosis revealed the same B-cell clones distribution than the one observed in blood with a dominant sIg D lambda population, a Genescan profile showing a major peak of 107 bp and a minor peak of 98 bp. Chromosomal analysis disclosed a 46,XX,del (10) (?p14) karyotype without detectable 7q deletion. To our knowledge, this observation represents the first reported case of biclonal low grade lymphoma hidden behind a normal classical kappa/lambda Ig light chain ratio in blood, but clearly demonstrated by the combination of three ancillary techniques (flow cytometry both analytical and cell sorting, molecular biology, and cytogenetics) and analysis of different tissues (i.e., in this case, lacrimal gland biopsy, blood, and bone marrow).

[Palpebral tumors: clinical and diagnostic considerations]. / Tumeurs palpébrales: aspects cliniques et diagnostiques.

The vast majority of palpebral tumors are benign and, when complete, straightforward excision is curative. In some cases, laser ablation can be appropriate. These tumors originate from the pilosebaceous adnexa of the skin and are mainly composed of cysts. For carcinomas, the extent of the tumoral expansion must be assessed on pathological examination of a specimen. In case of recurrence, the tumor may extend beyond the clinically visible borders. This is particularly true in the sclerodermiform type of basal cell carcinoma, which invades tissues deeply, in spindle cell carcinoma, which spreads within the thickness of the epidermis or the conjunctival epithelium, and in sebaceous gland carcinoma, which can present in a masquerade fashion.

[The ophthalmology department]. / Le Service d'Ophtalmologie.

The main clinical activities developed during the first 25 year of the department are described. Topics of fundamental and also clinical research are briefly reviewed.

Intranasal endoscopic surgery in traumatic optic neuropathy--the Belgian experience.

The management of traumatic optic neuropathy remains controversial. In this report we present the results of 8 patients treated by means of an intranasal endoscopic approach to the optic canal after at least 12 hours of corticosteroid therapy without improvement. Vision improved in four of the eight patients who underwent the surgery. There was no morbidity or mortality. As the results of the endoscopic optic nerve decompression are comparable to those reported using other surgical procedures, we feel that this approach merits consideration by surgeons.

Cytogenetic analysis of rare orbital tumors: further evidence for diagnostic implication.

INTRODUCTION. The pathologic diagnosis, and hence the management, of rare tumors of the orbit can represent a challenge. An increasing number of tumors have been shown to display specific chromosomal abnormalities detectable by cytogenetic analysis. MATERIALS AND METHODS. Two examples of rare primary orbital tumors are presented in which the correct pathologic diagnosis was either established or confirmed by cytogenetic analysis. Small pieces of the tumor were obtained at the time of biopsy and placed immediately, in a sterile fashion, in fresh culture medium. The cells were Giemsa stained and processed for chromosome analysis. RESULTS. In the first case, a 12-year-old boy was diagnosed with a sino-orbital mass after sustaining minor trauma. On biopsy, the pathologic examination was at first consistent with a Burkitt-like lymphoma, until cytogenetic analysis showed a t(8;21)(q22;q22) translocation, specific for granulocytic sarcoma, which corresponds to the localized solid form of acute myeloblastic leukemia. Consequently, proper chemotherapy was re-oriented and remission was achieved. In the second case, a 2-year-old boy presented with a well-vascularized orbital tumor. The histopathologic diagnosis of alveolar soft-part sarcoma of the orbit was confirmed by the finding of a specific t(X;17)(p11;q25) translocation. After two unsuccessful courses of chemotherapy, wide excision surgery with primary reconstruction brought remission. CONCLUSIONS. Cytogenetic analysis should be considered in the diagnosis of any orbital tumor which is suspected of malignancy.

Treatment of the postenucleation socket syndrome with a new hydroxyapatite tricalcium phosphate ceramic implant.

PURPOSE: Surgical correction of the postenucleation socket syndrome (PESS) is challenging. Various biomaterials are used for reconstruction of the anophthalmic orbit, often with unsatisfactory long-term results. Implants have been placed between the periorbital and the orbital floor. The authors describe a new material composed of hydroxyapatite tricalcium phosphate (HA-TCP) in the form of ceramic blocks, to be placed into the orbital fat as a new surgical site. METHODS: Ten patients with PESS underwent surgery to compensate the volume deficit of the anophthalmic orbit. Blocks of HA-TCP were created by fragmentation of a larger piece, tailored as needed, and implanted in the orbital fat. The patients were monitored regularly with clinical and radiologic examinations to evaluate the behavior of the implants. RESULTS: The volume of the HA-TCP was measured in 5 cases (mean, 2.95 +/- 1.08 ml). A significant reduction of enophthalmos was obtained: mean Hertel exophthalmometry measured 12.7 +/- 2.5 mm preoperatively and 14 +/- 2.4 mm postoperatively (p < 0.05). The average prosthesis volume was significantly reduced in the cases measured: 2.7 ml +/- 0.94 ml preoperatively and 1.8 +/- 0.7 ml postoperatively (p < 0.02). There was a negative correlation between the HA-TCP implant volume and postoperative prosthesis volume (correlation coefficient = -0.925; p < 0.05). According to photographic evaluation, correction of the enophthalmos and of the superior sulcus depression were obtained in 70% and 90% of cases, respectively. Magnetic resonance imaging seems to demonstrate that the blocks become well integrated into the surrounding orbital tissue. CONCLUSION: The HA-TCP blocks correct some anomalies of PESS. Placement of the blocks directly into the orbital fat is a promising alternative to the traditional subperiosteal location.

Multiple genetic loci modify risk for retinoblastoma in transgenic mice.

PURPOSE: Forty percent of cases of retinoblastoma, a childhood malignancy of the retina, are linked to the inheritance of a mutant allele of the retinoblastoma susceptibility gene Rb1. Tumor penetrance varies among carriers in different family pedigrees, indicating that other genetic factors may modify risk for occurrence of retinoblastoma. This study was undertaken to determine whether multiple genetic loci modify the risk for retinoblastoma in mice. METHODS: A line of alphaAcry-HPV16E6/E7 transgenic mice expressing the human papillomavirus type 16 E6 and E7 oncogenes (HPV-16 E6 and E7) ectopically in the retina was characterized. E6 and E7 proteins bind to and inactivate the cellular tumor suppressor proteins p53 and Rb, respectively. RESULTS: Retinoblastomas developed rarely when the alphaAcry-HPV16E6/E7 transgene was maintained on the FVB background, but tumors arose with high frequency on C57BL/6 X FVB and C3H x FVB F1 hybrid backgrounds. The incidence of retinoblastoma in the LHbeta-TAG transgenic mice, which express simian virus 40 large tumor antigen (SV40 T-ag), was also influenced by the FVB and C57BL/6 backgrounds. Resistance of the alphaAcry-HPV16E6/E7 FVB mice to retinoblastoma mapped in part to the retinal degeneration (rd) locus. However, multiple genetic experiments indicate that resistance to retinoblastoma depends on additional loci in FVB mice. CONCLUSIONS: Multiple cellular genes can modify risk for retinoblastoma in mice.

Trilateral retinoblastoma: insights into histogenesis and management.

Trilateral retinoblastoma (TRb) is a syndrome involving midline intracranial malignancies in children with the heritable form of retinoblastoma. All cases of TRb reported from 1971 to 1997 were reviewed. The histopathologic findings, clinical features, treatment modalities, and survival rates from 80 cases were evaluated. Histopathologic findings from intracranial malignancies demonstrated primitive neuroectodermal tumors in 61.5% of cases. Various degrees of neuronal or photoreceptor differentiation were seen in the other 38.5% of cases. Autopsy, histopathologic, and radiologic examinations did not show a more definitive site of origin of these intracranial tumors, although "pinealoblastoma" was often the diagnosis reported. These findings, together with analysis of the histopathologic similarities among human primitive neuroectodermal tumors, pinealoblastoma, retinoblastoma, and ependymoblastoma, suggest that TRb more likely arises from a germinal layer of predisposed primitive subependymal neuroblasts that are not necessarily destined for pineal or photoreceptor differentiation. Trilateral tumors have also been found in transgenic mice expressing the simian virus 40 T-antigen. Transgenic murine intracranial tumors are primitive neuroectodermal tumors arising from the subependymal layer. Transgenic mice with the murine interphotoreceptor cell binding protein promoter and simian virus 40 T-antigen also develop pineal tumors. Trilateral retinoblastoma is usually fatal, with an average survival time of 11.2 months. Therapies include radiation, systemic chemotherapy, intrathecal chemotherapy, and surgical resection/craniotomy in combination with radiation and/or chemotherapy. Survival may be prolonged with combination chemotherapy (24.6 months) and if neuroradiologic screening identifies TRb before symptoms are present (23.5 months). Recent success with platinum-based chemoreduction of intraocular retinoblastoma may indicate a similar role for platinum-based chemotherapy in the treatment of TRb. Routine central nervous system imaging should be considered in the management of TRb.

Treatment of proptosis with fat removal orbital decompression in Graves' ophthalmopathy.

PURPOSE: Retrospective evaluation of 41 proptosis reduction procedures using fat removal orbital decompression (FROD) according to a modified Olivari's technique. METHODS: Trans-septal excision of extraconal and intraconal fat was done under the microscope through the upper and lower eyelid blepharoplasty approach. Proptosis was measured with a Hertel exophthalmometer. RESULTS: Mean excision of 7.31 + 1.9 ml (range 3.25-12 ml) of orbital fat reduced proptosis on average by 4.7 + 2.4 mm (range 1-11 mm). Side effects were few, limited only to ocular motility disturbances. There was no significant effect on visual fileds. A postoperative drop in IOP was noted in patients with preoperative IOP above 21 mmHg. Efficient palpebral lengthening can be achieved with combined section of the levator aponeurosis horns in the upper eyelid, and/or auricular cartilage graft in the lower eyelid. CONCLUSIONS: FROD reduces proptosis in Grave's ophthalmopathy.

Pyoderma gangrenosum complicating Cogan's syndrome.

Cogan's syndrome is a rare clinical entity defined by the association of a nonsyphilitic interstitial keratitis and vestibuloauditory dysfunction, typically Menière's disease-like; the condition has been reported in association with a variety of cutaneous diseases. We now report a case of pyoderma gangrenosum complicating Cogan's syndrome in a 57-year-old woman, which then healed dramatically, as more interestingly did the associated uveitis with minocycline therapy.

Antineoplastic effect of 1,25-dihydroxy-16-ene-23-yne-vitamin D3 analogue in transgenic mice with retinoblastoma.

OBJECTIVE: To evaluate the in vivo efficacy and clinical toxic effects of the 1,25-dihydroxy-16-ene-23-yne-vitamin D3 analogue in beta-luteinizing hormone-Tag (LH beta-Tag) transgenic mice with heritable retinoblastoma. METHODS: Forty-two mice (8-10 weeks old), randomly assigned to experimental (n = 21) or control (n = 21) groups, received intraperitoneal injections of 0.05 microgram of 1,25-dihydroxy-16-ene-23-yne-D3 in 0.5-mL mineral oil vehicle (experimental group) or 0.5 mL of mineral oil vehicle (control group) for 5 weeks. One experimental and 3 control animals died of injection-related trauma. Eyes were enucleated 1 week after treatment and were examined histologically in a masked fashion. RESULTS: All experimental and control animals showed evidence of tumor. The tumors in the experimental mice showed a significantly smaller cross-sectional area (0.88 +/- 0.08 mm2) compared with that in the control mice (1.12 +/- 0.12 mm2) (P = .02). All mice completed the treatment and showed no clinical evidence of toxic effects. CONCLUSIONS: Tumors in transgenic mice with retinoblastoma treated with 1,25(OH)2-16-ene-23-yne-D3 showed a 21% smaller cross-sectional area compared with that in the control mice, without producing clinically apparent toxic effects. This compound may be useful as adjunctive therapy in the treatment of retinoblastoma.

Trilateral tumors in four different lines of transgenic mice expressing SV40 T-antigen.

PURPOSE: A line of transgenic mice containing the simian virus (SV) 40 T-antigen (T-ag) gene driven by the beta-luteinizing hormone (BLH) promoter developed bilateral retinoblastoma and primitive neuroectodermal tumors (PNET) of the midbrain. Midbrain tumors arose from the subependymal layer of the cerebral aqueduct. Bilateral ocular and brain tumors ("trilateral") were found in three other SV40 T-ag transgenic murine lines containing different promoters (murine interphotoreceptor retinoid-binding protein (IRBP), human IRBP, and alpha A-crystallin). To gain insight into the regulatory mechanisms involved in central nervous system tumorigenesis, the authors examined brain tumors from four lines of SV40 T-ag mice with different promoters. METHODS: Formalin-fixed brain tumors were examined from four lines of transgenic mice containing different promoters linked to the protein coding region of the enhancerless SV40 T-ag oncogene. Transgenes contained the following promoters: BLH, mouse 1.8-kb IRBP, human 1.3-kb IRBP, and alpha A-crystallin. RESULTS: Mice with a 1.8-kb IRBP promoter develop retinal photoreceptor and pineal tumors. Intracranial tumors arising from the subependymal layer of the third ventricle also were observed. Mice with a 1.3-kb IRBP promoter exhibit bilateral retinal PNET and PNET originating from the subependymal layer of the third ventricle. Mice with the alpha A-crystallin promoter exhibit bilateral lens tumors and PNET of the midbrain. CONCLUSIONS: Ocular tumors in these mice may be ascribed to the promoter-driven, tissue-specific expression of SV40 T-ag. The common finding of PNET arising from the subependymal layer of the diencephalon is unlikely to be promoter related. These findings indicate that a regulatory region specific to the subependymal layer of the cerebral aqueduct and third ventricle resides in the structural region of the SV40 T-ag gene.

Apoptosis or retinoblastoma: alternative fates of photoreceptors expressing the HPV-16 E7 gene in the presence or absence of p53.

A transgenic mouse model for retinoblastoma was produced previously by directing SV40 T antigen expression to retinal photoreceptor cells using the promoter of the interstitial retinol-binding protein (IRBP) gene. This gene becomes active prior to the terminal differentiation of photoreceptors. Because T antigen-transforming activity is attributable, at least in part, to the inactivation of the retinoblastoma (pRb) and p53 tumor suppressor proteins, we addressed the role of p53 in the development of retinoblastoma in mice. Transgenic mice expressing HPV-16 E7 under the control of the IRBP promoter were generated to inactivate pRb in photoreceptors while leaving p53 intact. Rather than developing retinoblastomas, the retinas of these mice degenerate due to photoreceptor cell death at a time in development when photoreceptors are normally undergoing terminal differentiation. The dying cells exhibit the histological and ultrastructural features of apoptosis and contain fragmented DNA. p53 is required for the induction of apoptosis in this model, because mice expressing E7 in a p53 nullizygous background develop retinal tumors instead of undergoing retinal degeneration.

Photoreceptor cell tumors in transgenic mice.

PURPOSE: To produce transgenic mice that express the SV40 T-antigen oncogene specifically in photoreceptor cells, giving rise to retinoblastoma tumors of photoreceptor cell origin; to characterize the mice with regard to transgene expression and pathology and to characterize the resulting tumors histologically. METHODS: Transgenic mice were generated that express T-antigen under the control of the murine interstitial retinol binding protein promoter. RESULTS: All mice produced developed either ocular or intracranial tumors, or both, at an early age. One line of mice was generated, and all mice of this line develop both retinal photoreceptor cell and pineal tumors by as early as 2 weeks of age. Cell lines have been established from both tumor types. CONCLUSIONS: These mice represent an animal model system for human trilateral retinoblastoma, in which retinoblastomas are accompanied by pineal tumors.