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Joel M Mor,1 Alexander C Rokohl,1 Konrad R Koch,1 Ludwig M Heindl1,21Department of Ophthalmology, University of Cologne, Cologne, Germany; 2Center for Integrated Oncology (CIO) Aachen-Bonn-Cologne-Duesseldorf, Ophthalmic Oncology Unit, Cologne, GermanyPurpose: To evaluate the role of sentinel lymph node biopsy (SLNB) in conjunctival melanoma (CM).Methods: This article provides a review of the literature from PUBMED.Results: Data on SLNB in the management of CM are scarce and only two relatively large cohorts have been reported. Although indication criteria for SLNB vary slightly, positive findings can be expected in 11%–13% of CM cases, including small tumors. False negative SLNB findings are rare (

OBJECTIVES: This study investigated the birth outcomes of Japanese Americans, focusing on the role of the mother's place of birth. METHODS: Single live births to US-resident Japanese American mothers (n = 37,941) were selected from the 1983 through 1987 US linked live birth-infant death files. RESULTS: US-born mothers were more likely than foreign-born mothers to be less than 18 years old and not married, to start prenatal care early, and to more adequately use prenatal care. Infants of foreign-born Japanese Americans had a slightly lower risk of low birthweight. No significant differences were found between nativity groups for very low birthweight or neonatal, postneonatal, and infant mortality. The mortality rates of infants of US-born (6.2) and foreign-born (5.4) Japanese American women were below the US Year 2000 objective but still exceeded Japan's 1990 rate (4.6). However, low-birthweight percentages of the US-born group (5.7%) and the foreign-born group (5.0%) were similar to that of Japan (5.5%). CONCLUSIONS: The infants of foreign-born Japanese-American women exhibited modestly better low-birthweight percentages than those of US-born Japanese Americans. This finding supports theories of the healthy immigrant. [ABSTRACT FROM AUTHOR]

This study examined the impact of maternal diabetes on birth weight for gestational age patterns of all term black infants and white infants in the United States using data derived from the 1990-1991 US Live Birth File of the National Center for Health Statistics. Infants of both black mothers and white mothers exhibited the expected fetal overgrowth associated with maternal diabetes. However, the increase in birth weight was much greater in infants of black than white diabetic mothers in comparison with their nondiabetic counterparts, as measured by the discrepancy in birth weight between infants of diabetic and nondiabetic mothers at each gestational week, the incidence of large for gestational age, high birth weight, small for gestational age, and low birth weight. After adjustment for maternal hypertension, prenatal care use, and sociodemographic factors, the disparity in mean birth weight associated with diabetes was 211.67 g in black infants and 115.74 g in white infants. The adjusted odds ratios of birth weight > or = 4,000 g were 2.98 (95% confidence interval 2.89-3.12) for black infants and 1.83 (95% confidence interval 1.78-1.89) for white infants. Given the potential risks for mothers and infants consequent to maternal diabetes and fetal hyperinsulinemia, further investigation of the prevalence, characteristics, and outcomes of diabetes during pregnancy among black mothers and infants is warranted. [ABSTRACT FROM AUTHOR]

Purpose: The Risk of Pediatric and Adolescent Cancer Associated with Medical Imaging (RIC) Study is quantifying the association between cumulative radiation exposure from fetal and/or childhood medical imaging and subsequent cancer risk. This manuscript describes the study cohorts and research methods., Methods: The RIC Study is a longitudinal study of children in two retrospective cohorts from 6 U.S. healthcare systems and from Ontario, Canada over the period 1995-2017. The fetal-exposure cohort includes children whose mothers were enrolled in the healthcare system during their entire pregnancy and followed to age 20. The childhood-exposure cohort includes children born into the system and followed while continuously enrolled. Imaging utilization was determined using administrative data. Computed tomography (CT) parameters were collected to estimate individualized patient organ dosimetry. Organ dose libraries for average exposures were constructed for radiography, fluoroscopy, and angiography, while diagnostic radiopharmaceutical biokinetic models were applied to estimate organ doses received in nuclear medicine procedures. Cancers were ascertained from local and state/provincial cancer registry linkages., Results: The fetal-exposure cohort includes 3,474,000 children among whom 6,606 cancers (2394 leukemias) were diagnosed over 37,659,582 person-years; 0.5% had in utero exposure to CT, 4.0% radiography, 0.5% fluoroscopy, 0.04% angiography, 0.2% nuclear medicine. The childhood-exposure cohort includes 3,724,632 children in whom 6,358 cancers (2,372 leukemias) were diagnosed over 36,190,027 person-years; 5.9% were exposed to CT, 61.1% radiography, 6.0% fluoroscopy, 0.4% angiography, 1.5% nuclear medicine., Conclusion: The RIC Study is poised to be the largest study addressing risk of childhood and adolescent cancer associated with ionizing radiation from medical imaging, estimated with individualized patient organ dosimetry., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: In contrast to cutaneous melanoma, there are no uniform guidelines regarding surveillance of ocular (uveal, conjunctival) melanomas. A consented standard operating procedure (SOP) by the "Netzwerk onkologische Spitzenzentren" Germany only exists for conjunctival melanoma but not for uveal melanoma. Surveillance is partially based on German S3-guidelines for cutaneous melanoma and is carried out by oncologic centres in a multidisciplinary approach. This study aims to evaluate patients' adherence to surveillance programs and whether surveillance recommendations (examinations, intervals) can be realised., Methods: Retrospective analysis of all ocular melanoma patients overseen at the University Hospital of Cologne between 2008 and 2019. The study evaluates rates of successful patient integration into a standardized surveillance program and patients' surveillance adherence, subject to age, gender, primary therapy and tumour entity, respectively., Results: 99 patients were included (56 female, 43 male), 83 of which had uveal melanomas and 16 conjunctival melanomas. Mean follow-up was 59 months. 81% of patients were integrated into a surveillance program. Surveillance was performed according to published recommendations in 78%. 13% of patients dropped out of the surveillance program after a mean period of 38 months., Conclusions: Our data show a growing number of patients in standardized surveillance. However, there are still gaps. There is a need for guidelines specifically designed for ocular melanomas, allowing centres to offer patients an individualized approach., Competing Interests: The authors declare that they have no conflict of interest./Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 19 (COVID-19) has led to a worldwide pandemic. This pandemic presents a huge challenge for the healthcare system and also for ophthalmologists. Previous studies and case reports indicated that SARS-CoV‑2 also infects the conjunctiva resulting in conjunctivitis. In addition, infectious virus particles in the tear fluid can be potential sources of infection; however, the detection of SARS-CoV‑2 RNA in the tear fluid has rarely been successful. Although isolated conjunctival involvement is highly unlikely, at the current point in time of the COVID-19 pandemic, practically every patient examined by an ophthalmologist could be infected with SARS-CoV‑2. Therefore, protective and hygiene measures should currently be consistently followed to minimize the risk of spreading the virus. Currently, there are no treatment recommendations for conjunctivitis associated with COVID-19. Tear substitutes might be helpful for symptom relief but there is no evidence for a topical antiviral therapy. In the future ophthalmologists could play a decisive role in the screening of maculopathies that might occur during COVID-19 treatment using chloroquine or hydroxychloroquine.

Objectives: To assess symptoms and signs of the dry anophthalmic socket syndrome (DASS) in a standardized manner., Methods: 87 unilateral anophthalmic patients were evaluated using the Ocular Surface Disease Index (OSDI), the 5-Item Dry Eye Questionnaire (DEQ-5), and a modified version of Symptom Assessment iN Dry Eye (SANDE) questionnaire separately for the anophthalmic socket and for the healthy fellow eye. Conjunctival inflammation was semi-quantitatively graded and Schirmer I test with topical anesthesia was performed bilaterally. The correlations between scores of the dry eye questionnaires and the results of the Schirmer tests, conjunctival inflammation, and demographic data were examined., Results: Patients had significantly higher OSDI, DEQ-5 and SANDE scores at the anophthalmic side compared to the healthy eye (p ≤ 0.019, respectively). 63% of patients complained of anophthalmic socket dryness in at least one of the three questionnaires. Patients had higher inflammation (p < 0.001) and more tear volume in the Schirmer I test with topical anesthesia (p ≤ 0.024) on the anophthalmic side compared to the fellow eye., Conclusions: Most anophthalmic patients have significantly more subjective dryness complaints on their anophthalmic side compared to the healthy fellow eye, even in absence of tear deficiency and clinical blepharitis. Eye care practitioners should consider the diagnosis criteria and the definition for DASS proposed in this study, when counseling anophthalmic patients. However, research should be undertaken to investigate the role and the interactions of causative etiological causes for DASS. Furthermore, there is a high priority to establish a standardized examination protocol and to develop an evidence-based treatment algorithm for DASS., Competing Interests: Declaration of competing interest All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter discussed in the manuscript. All authors have full control of all primary data and they agree to allow Ocular surface to review their data upon request., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The aim of this article is to provide an overview on the current state of personalized medicine in the systemic treatment of selected periocular tumors, such as basal cell carcinoma, Merkel cell carcinoma and conjunctival melanoma. This article therefore provides an extensive current literature review from PubMed including the current guidelines and standard operating procedures (SOP). As 90% of basal cell carcinomas have a pathologic activation of the sonic hedgehog pathway, vismodegib is a new treatment option for inoperable or metastatic basal cell carcinoma and for patients with Gorlin-Goltz syndrome. A novel approach of systemic medicine for the treatment of metastatic Merkel cell carcinoma is immunotherapy using the immune checkpoint inhibitor avelumab. Other personalized immunotherapies, such as the checkpoint inhibitors pembrolizumab and nivolumab, the tyrosine kinase inhibitor pazopanib and the role of the hedgehog pathway in Merkel cell carcinomas are the subject of current research and will certainly play an important role in future treatment. In the narrow sense personalized medicine has only come true for metastatic conjunctival melanomas: systemic treatment with BRAF, MEK and/or checkpoint inhibitors is initiated only when a BRAF mutation is detected in the tumor or metastatic tissue. Systemic immunotherapy with the checkpoint inhibitors pembrolizumab and nivolumab can also be used as a treatment option in metastatic conjunctival melanomas. In summary, personalized medicine is a subject of current research and provides many new targeted treatment options especially for periocular malignancies; however, it also involves many great challenges in the development and implementation of new techniques and therapies.

Benign tumors of the ciliary body are rare and may potentially be confused with uveal melanoma in clinical routine. Clinical findings rarely allow for safe differentiation. Hence primary excisions are frequent. We report the case of a patient with a benign ciliary tumor, which was observed over a total of 13 years and eventually underwent a local tumor resection.

Background: The three-dimensional surface imaging system is becoming more common in plastic surgeries. However, few studies have assessed three-dimensional periocular structures and surgical outcomes. This study aimed to propose a standardized three-dimensional anthropometric protocol for the periocular region, investigate its precision and accuracy, and determine the three-dimensional periocular anthropometric norms for young Caucasians., Methods: Thirty-nine healthy young Caucasians (78 eyes) were enrolled. Three-dimensional facial images were obtained with a VECTRA M3 stereophotogrammetry device. Thirty-eight measurements in periocular regions were obtained from these images. Every subject underwent facial surface capture twice to evaluate its precision. A paper ruler was applied to assess its accuracy., Results: Sixty-three percent of measurements in linear distances, curvatures, angles, and indices were found to reach a statistically significant difference between sexes (p ≤ 0.05, respectively). Across all measurements, the average mean absolute difference was 0.29 mm in linear dimensions, 0.56 mm in curvatures, 1.67 degrees in angles, and 0.02 in indices. In relative error of magnitude, 18 percent of the measurements were determined excellent, 51 percent very good, 31 percent good, and none moderate. The mean value of the paper-ruler scale was 10.01 ± 0.05 mm, the mean absolute difference value 0.02 mm, and the relative error of magnitude 0.17 percent., Conclusions: This is the first study to propose a detailed and standardized three-dimensional anthropometric protocol for the periocular region and confirm its high precision and accuracy. The results provided novel metric data concerning young Caucasian periocular anthropometry and determined the variability between sexes.

The gold standard for the treatment of periocular basal cell carcinoma is surgical resection followed by ophthalmoplastic reconstruction. The highest priority in most cases is the complete histopathologically controlled tumor excision. The histopathological preparation can be carried out in two stages by rapid overnight embedding or intraoperatively by a rapid frozen section procedure. A variety of reconstruction methods enable a customized and in most cases also a cosmetically and functionally attractive defect coverage. Postoperatively, a regularly performed tumor aftercare is essential.

Background: A space-occupying lesion of the eyelid in young adults is often a sign of an inflammation, a trauma or a benign neoplasm. The aim of this case report is to demonstrate a rare basal cell carcinoma, which presumably already arose in adolescence without further high-risk factors., Methods: A 28-year-old male patient presented for a second opinion on a painless swelling of the right lower eyelid. According to the patient's history the swelling had been present since the age of 16 years and originally resembled a molluscum contagiosum. An ophthalmologist in private practice made the diagnosis of a suspected trichoepithelioma. The extended patient history revealed a blood coagulation disorder. The clinical ophthalmological examination revealed a nodular space-occupying lesion with a border wall and telangiectasia. The further ophthalmological examination was bilaterally inconspicuous. Due to the suspicion of a malignant process, an operation was promptly carried out using local anesthesia with complete tumor excision and pedicled flap plasty as well as a histopathological investigation to confirm the diagnosis., Results: The histopathological investigation revealed underlying infiltrates of a basaloid tumor with bale-shaped trabecular growth, sometimes with peripheral palisading of the cells. The cells were predominantly monomorphic with isolated pleomorphic nuclei and sometimes enclosed mitoses. Immunohistochemically the cells were strongly positive for BerEP4 and negative for epithelial membrane antigen (EMA). The diagnosis of a nodular basal cell carcinoma of the right lower eyelid was made. All incision margins were free of tumor cells (R0 resection). In the dermatological screening no further manifestations were detected., Conclusion: Despite the occurrence of a space-occupying lesion of the eyelid in a young adult patient and also with no further risk factors, in addition to an inflammatory event and a benign tumor, a malignant disease, such as a basal cell carcinoma should also be taken into consideration. A tissue biopsy or complete excision with subsequent histological examination including an immunohistochemical analysis are essential for differentiation from other tumor entities.

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

The development of microendoscopes in lacrimal drainage surgery has led to the introduction of novel surgical procedures that maintain transcanicular anatomy, including a variety of lacrimal drainage intubation systems. Depending on the location and extent of the lacrimal duct stenosis, bicanaliculoanular, monocanalicular, monocanaliculonasal, bicanalicular, and bicanaliculonasal intubation techniques and systems, as well as a combination of these, may be used. For isolated intubation of the puncta lacrimalia, perforated punctum plugs may be used, while pure monocanalicular intubation can be performed using a Mini-Monoka. The monocanaliculonasal intubation systems include the Monoka (Wide Collarette type), Monoka of Fayet (Crawford type), the self-threading Monoka (Ritleng type), the Masterka, and the LacriJet for the ophthalmic surgeon. The bicanaliculonasal intubation systems include various BIKA systems, the Ritleng intubation system, the Crawford intubation system, and the FCI Nunchaku. Indications for both monocanaliculonasal and bicanaliculonasal intubation systems are obstructions, stenoses or lacerations of all kinds, as well as obstructions and stenoses after opening or after a DCR. For a conjunctivodacryocystorhinostomy (CDCR), the classical Lester Jones Tube, Metaireau Tubes, and StopLoss Jones Tube may be used. Although the study situation is ambiguous and therefore lacrimal drainage intubation is not considered mandatory, most ophthalmic surgeons do not forego intubation - despite the higher costs and slightly more protracted surgery. The surgeons' selection of the intubation system depends on the chosen form of intubation, costs and personal preferences and experience., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

In Germany, Austria, and Switzerland, over 90% of ocularists still manufacture customized prostheses using cryolite glass from Thuringia. The present manuscript demonstrates this long-forgotten technique in detail. This manuscript shows some major advantages of manufacturing prosthetic eyes using cryolite glass in comparison to poly(methyl methacrylate) (PMMA). These advantages include a lighter weight of the prosthesis, higher levels of patient satisfaction, and only one appointment necessary for the customized manufacturing. Potential risk of breakage seems not to be a critical disadvantage for glass prosthetic eye wearers. However, in some patients, manufacturing a well-fitting prosthetic eye is not possible or reasonable due to anophthalmic socket complications such as post nucleation socket syndrome, scarred fornices, or an orbital implant exposure. This article gives ophthalmologists a better insight into ocularistic care in order to improve the essential interprofessional collaboration between ocularists and ophthalmologists.

Purpose: To investigate mucoid discharge and the inflammatory response of anophthalmic sockets to cryolite glass prosthetic eye wear., Patients and Methods: A total of 101 cryolite glass prosthetic eye wearers used visual analog scales (0-10) to measure frequency, color, volume, and viscosity of mucoid discharge associated with their prosthesis. Standardized photographs of the conjunctiva of their anophthalmic sockets were taken and conjunctival inflammation was semi-quantitatively graded (0-4). All characteristics of discharge and conjunctival inflammation were correlated to eye loss cause, hand washing behavior, and cleaning regimes as explanatory variables., Results: Mean mucoid discharge characteristics (0-10 scale) were frequency 5.3 ± 2.8, color 4.8 ± 3.2, volume 4.9 ± 3.0, and viscosity 5.1 ± 3.2. The mean conjunctival inflammation score (0-4 scale) was 2.1 ± 1.0. There was a positive correlation between the grade of conjunctival inflammation and the frequency (p = 0.018), color (p = 0.001), volume (p = 0.003), and the viscosity of mucoid discharge (p = 0.005). More conjunctival inflammation was associated with higher frequency of cleaning (p < 0.001) and lower frequency of hand washing before removal (p = 0.001). Higher frequency, color, volume, and viscosity of discharge were associated with higher frequency of cleaning (p ≤ 0.001)., Conclusions: Discharge severity associated with prosthetic eye wear was positively correlated with more conjunctival inflammation, higher cleaning frequency, and less hand washing before handling. The results suggest that cryolite glass eyes should not be removed daily for cleaning and that further research should be undertaken to develop a standardized treatment protocol for managing inflammation and mucoid discharge. This protocol would advise hand washing before handling cryolite glass eyes and recommend a minimum period of wear between cleaning sessions.

Background: The differentiation of iridic space-occupying lesions represents a regularly reoccurring diagnostic challenge., Objective: This article presents an overview of the epidemiological data and describes the diagnostic procedure for iris tumors., Material and Methods: The article provides a review of the literature from PubMed and own clinical results., Results: Melanocytic lesions comprise the vast majority of all iris tumors and include nevi and melanomas. Slit lamp biomicroscopy with standardized photography reveals two-dimensional planar tumor growth over time, which is the only recognized clinical surrogate finding for a malignant event. Ultrasound biomicroscopy (UBM) is additionally obligatory because it is the only method which enables documentation of the extent of tumor penetration, ciliary body involvement and internal structure of iris tumors., Conclusion: Serial slit lamp and UBM examinations with reproducible pupillary diameters are indispensable for the differentiation of cystic, solid and tumor-simulating lesions and for the detection of malignant transformation in iris tumors.

Background: Benign iridal tumors rarely necessitate a therapeutic intervention. In contrast, malignant tumors of the iris can threaten the patient's life and eyesight and require early treatment to prevent the development of metastases., Objective: Presentation of current treatment options for iridal tumors with special emphasis on iridal melanoma., Methods: This article gives an overview of the current literature based on a PubMed search as well as own clinical experience., Results: Treatment options for iridal and ciliary body melanomas comprise radiotherapeutic and surgical (eyeball-sparing and non-sparing) approaches. The eyeball-sparing surgical procedure of choice is block excision. While local tumor control rates and metastasis rates of block excision and radiotherapy are comparable, there are distinct differences especially between the spectra of complications. New treatment procedures include immunomodulatory approaches and targeted therapies. Using checkpoint inhibitors, no convincing enhancement of overall survival could be demonstrated for metastatic iridal melanoma, as is the case for cutaneous melanoma. In contrast, tumor vaccination with the help of tumor RNA-laden patient-derived dendritic cells seems to be a promising option for a subgroup of high-risk patients. Targeted therapies aiming to suppress the MAPK and PI3K/Akt pathways could not achieve any improvement in patient survival., Conclusion: For the primary treatment of iridal melanoma a surgical, eyeball-sparing approach and also when appropriate, radiotherapy can be recommended. In the future, eligible high-risk patients could profit from a tumor vaccination. To date, there is no effective systemic treatment for metastatic iridal melanoma.

Background: A smooth supply with a visually appealing prosthetic eye after enucleation is not just a cosmetic solution, it is also a key factor in successful social and psychological rehabilitation., Objectives: This article provides an overview of the current state of medical and ocular care regarding prosthetic eyes in Germany. It focuses mainly on the newest clinical results, daily care, complications, and psychological aspects of wearing prosthetic eyes., Methods: The study is comprised of the newest clinical results and a current PubMed literature review., Results: In Germany, enucleated patients normally get a double-walled, hollow prosthetic eye made of cryolite glass, and patients with a microphthalmic or phthisic eye receive a thin single-walled prosthesis. Anophthalmic patients wearing cryolite glass prosthetic eyes seem to be more satisfied with their appearance and the look of their prostheses than polymethylmethacrylate (PMMA) prosthetic eye wearers. Cryolite glass prosthetic eyes must be renewed at least each year, while PMMA prostheses need to be polished once a year and renewed after five years of wearing. Among children, the fit of the prosthetic eye must be checked, based on growth, semi-annually. A slightly higher risk of breakage of cryolite glass prostheses is, for most patients, not a great disadvantage in everyday life. Ocularists and ophthalmologists should determine an individual cleaning regime, together with the patient, that is dependent on the material of the ocular prosthesis and other external factors. Complications, such as allergic, giant papillary, viral and bacterial conjunctivitis and blepharoconjunctivitis sicca must be treated at an early stage to allow for a prosthetic eye. In the case of inflammation-caused socket shrinkage or post-enucleation socket syndrome, surgical interventions are needed to re-enable the use of a prosthetic eye. Since the health of the remaining eye is the major psychological burden of prosthetic eye wearers, good ophthalmological care and medical screenings are essential elements., Conclusions: A smooth supply with a prosthetic eye, adequate and early treatment of possible complications and attention to psychological aspects is essential for successful long-term rehabilitation of enucleated patients., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: External dacryocystorhinostomy (DCR) is considered as the gold standard in the treatment of acquired nasolacrimal duct obstruction. However, many advances have been made towards the development of modern minimally invasive therapies. These new techniques were proven less harmful to the patients' skin and medial palpebral structures with their palpebral-canalicular pump mechanism. Options include endonasal and transcanalicular procedures. Here, we report on our 2-year experience with the surgical technique, results and complications of transcanalicular laser-assisted DCR., Methods: This is a retrospective study. A total of 104 patients with acquired nasolacrimal duct obstruction underwent transcanalicular laser-assisted DCR combined with bicanalicular silicon intubation. We then analyzed intra-/post-operative complications and subjective and objective success rates. The institutional ethics committee ruled that approval was not necessary. The trial was registered with the German Clinical Trials Register (DRKS00012879)., Results: Transcanalicular laser-assisted DCR in combination with bicanalicular silicon intubation could be performed surgically successfully in 101 patients (97%). In three cases (3%) using the superior canalicular approach, positioning of the laser instrument at the anteroinferior rim of the middle turbinate failed. Complications included thermal injury to the canaliculus (one), canalicular infection (two) and silicon tube prolapse (ten). Functional success (resolution of preoperative symptoms) was achieved in 80 cases (77%), functional failure occured in 24 cases with all patients reporting persisting epiphora, 15 reporting failure to irrigate the nasolacrimal duct and 15 requiring secondary external DCR., Conclusions: Laser-assisted DCR shows promising results with few complications. It seems well suited as a second-step procedure after failed recanalization and before external DCR.

Background: CyberKnife® stereotactic radiosurgery is a new treatment option for uveal melanoma., Objective: This review outlines the technique of robot-assisted CyberKnife® therapy, as well as the pros and cons in the treatment of uveal melanoma., Methods: The study provides a PubMed literature review and own preliminary clinical experiences., Results: CyberKnife® therapy for choroidal and ciliary body melanomas shows comparable results concerning local tumor control and overall survival matching those of conventional therapies. With only low complication rates, a high level of quality of life can be conserved by possible preservation of visual acuity as well as the ocular globe., Conclusion: Stereotactic radiosurgery using CyberKnife® seems to be an efficient and safe therapeutic option for malignant melanomas affecting the choroid and ciliary body. Comparative studies with conventional radiation strategies are now a high priority.

The most common iris lesions are iris nevi, iris melanomas and iris pigment epithelium cysts. However, there is an abundance of rare differential diagnoses that have to be considered, including other melanocytic and non-melanocytic lesions. Diagnostic tools include the slit lamp examination, gonioscopy, tonometry, transillumination, ultrasound biomicroscopy (UBM), optical coherence tomography, fluorescein angiography and standardized photography-assisted documentation. The timely identification of malignant lesions (i.e. iris melanoma) is paramount. To assess malignancy criteria of iris nevi, the ABCDEF rule (age young, blood, clock hour inferior, diffuse growth, ektropion uveae, feathery margins) can be applied. Statistically, up to 11% of iris nevi may develop into iris melanomas within 20 years. TNM Staging follows the 2010 AJCC cancer staging manual and helps determine the optimal treatment strategy. Treatment options include radiotherapy, such as plaque brachytherapy and proton beam radiation therapy, as well as surgical excision. Both the surgical and the radiotherapeutic approaches show comparable local tumor control rates. However, the spectrum of therapy-related side effects and complications may differ amongst treatment modalities. After initial treatment, patients should be followed up every 3 - 6 months. Tumor-related mortality ranges between 0 - 11% and is significantly lower than in other uveal melanomas. A prognostic value of common genetic alterations, which have been identified as significant prognostic factors in posterior uveal melanoma, could not be shown for iris melanoma., Competing Interests: Interessenkonflikt: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Today's gold standard in the treatment of infrasaccal primary acquired nasolacrimal duct obstruction (PANDO) is external dacryocystorhinostomy (DCR), a relatively invasive procedure that can be performed after failure of recanalizing treatments. However, with progress in the field of diode laser technology, new approaches have emerged. Laser-assisted transcanalicular DCR with subsequent bicanalicular silicon intubation is a new option showing great promise as a viable minimally invasive procedure. Under permanent endoscopic visual control from the nasal cavity, a diode laser fiber is inserted into the lacrimal sac and laser energy is applied to create a bony ostium between the lacrimal sac and the nasal cavity. Since no skin incision needs to be made, advantages of this method comprise the sparing of the skin as well as the medial palpebral structures and the physiological palpebral-canalicular pump mechanism. The duration of surgery as well as reconvalescence is generally shorter than with external DCR. Complications include silicon tube prolapse, mild swelling and, rarely, canalicular infection and thermal injury. One-year functional success rates, defined as complete resolution of symptoms and ostium patency, are high, yet still range behind those of external DCR. However, secondary external DCR after failure of laser-assisted DCR can be performed without difficulty. Thus, laser-assisted transcanalicular DCR is a valid option that should be considered as a second-step procedure after failure of recanalization procedures and before external DCR.

Aim: In this review, we outline similarities between conjunctival and skin melanoma as well as the effectiveness of combined BRAF/MEK inhibition in melanoma, and discuss the applicability of these agents in conjunctival melanoma., Methods: The study provides a PubMed literature review., Results: Conjunctival melanoma and skin melanoma are genetically and phenotypically related. Both tumors typically harbor BRAF mutations in more than 50% of cases. New targeted therapies in metastatic skin melanoma include selective inhibition of BRAF and MEK. Combined BRAF/MEK inhibition has revolutionized the treatment of metastatic skin melanoma, significantly improving patients' prognoses. While these new substances have been investigated extensively in the treatment of skin melanoma, comparable studies in conjunctival melanoma do not exist owing to the rarity of the malignancy., Conclusions: The application of combined BRAF/MEK inhibition in metastatic or unresectable conjunctival melanoma shows great potential for improving patients' prognoses. Future studies are needed to investigate the assumed benefit.

Dissemination of cancer cells from primary to distant sites is a complex process; little is known about the genesis of metastatic changes during disease development. Here we show that the metastatic potential of E2F1-dependent circulating tumour cells (CTCs) relies on a novel function of the hyaluronan-mediated motility receptor RHAMM. E2F1 directly up-regulates RHAMM, which in turn acts as a co-activator of E2F1 to stimulate expression of the extracellular matrix protein fibronectin. Enhanced fibronectin secretion links E2F1/RHAMM transcriptional activity to integrin-β1-FAK signalling associated with cytoskeletal remodelling and enhanced tumour cell motility. RHAMM depletion abolishes fibronectin expression and cell transmigration across the endothelial layer in E2F1-activated cells. In a xenograft model, knock-down of E2F1 or RHAMM in metastatic cells protects the liver parenchyma of mice against extravasation of CTCs, whereas the number of transmigrated cells increases in response to E2F1 induction. Expression data from clinical tissue samples reveals high E2F1 and RHAMM levels that closely correlate with malignant progression. These findings suggest a requirement for RHAMM in late-stage metastasis by a mechanism involving cooperative stimulation of fibronectin, with a resultant tumourigenic microenvironment important for enhanced extravasation and distant organ colonization. Therefore, stimulation of the E2F1-RHAMM axis in aggressive cancer cells is of high clinical significance. Targeting RHAMM may represent a promising approach to avoid E2F1-mediated metastatic dissemination., (Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Background: We report the prevalence of diabetes in a rural, multiethnic community in Hawaii, of predominantly Asian and Native Hawaiian ancestry, by using 1997 World Health Organization diagnostic criteria applied to a two-hour oral glucose tolerance test., Methods: This cross-sectional survey included 1452 men and nonpregnant women who were >18 years of age. Blood was drawn in the fasting and postchallenge states. Individuals under pharmacologic treatment for diabetes were excluded. Information obtained included demographics, medical history, dietary intake, physical activity, and anthropometric measurements., Results: Prevalence of diabetes was approximately three-fold higher among Asian and Native Hawaiian ancestry groups than among Caucasians, even after adjusting for other risk factors. Furthermore, diabetes prevalence was similar among all non-Caucasian ethnic groups despite significant differences in body mass indices., Conclusions: These findings indicate that earlier reports of high prevalence of diagnosed diabetes among Asians and Hawaiian ethnic groups were not due to detection bias, since our study revealed similar prevalence of previously unrecognized diabetes. Furthermore, similar prevalence among these groups was observed despite significant differences in body mass indices, diet, and physical activity. This apparent paradox may reflect limitations in the measurement of these risk factors; differences in the impact of these risk factors on diabetes risk in different ethnic groups; or ethnic differences in lifestyle, biochemical, or genetic factors that were not examined in this study.

Objectives: Recent studies have suggested that heart-rate corrected QT interval (QTc) in normal populations may be influenced by genetic factors. We report findings of a study of the relationship between QTc, increased QTc (> 440 ms) and angiotensin-converting enzyme (ACE) genotype in a multiethnic, population-based study completed in rural Hawaii., Methods: Blood samples were obtained while fasting and after an oral glucose challenge from 1452 individuals between 1997 and 2000. The clinical examination included an electrocardiogram. Medical histories, behavioral and socio-demographic information were obtained during the interview. Ethnicity was estimated by self-report. The insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene was determined by polymerase chain reaction (PCR) from a random sample of 588 participants. Multiple linear and logistic regression was used to test for associations between QTc and ACE gene polymorphisms., Results: The overall crude prevalence of increased QTc was 21.2%. The prevalence of increased QTc was lowest among those with ACE DD genotype, and highest among those with ACE insertion/insertion (II) genotype. The adjusted odds ratio for increased QTc was 2.29 (95% CI 1.02-5.12) and 3.61 (95% CI 1.60-8.13) for ID and II genotypes, respectively, compared to the DD genotype. The test for trend was highly significant (p < 0.001)., Conclusions: The ACE insertion allele was associated with increased prevalence of prolonged QTc independent of ethnicity, age, gender, and BMI. These findings may implicate the ACE gene as an important genetic risk factor for cardiovascular disease morbidity and mortality.

In the state of Hawaii, Samoan mothers are known for the large average birthweight and low percentage of low birthweight (< 2500 g) of their infants, in spite of the relatively low socio-economic status of the population. This paper reports the findings of a temporal trend analysis of birth outcomes of Samoan women and identifies worrying changes. Data were obtained from Hawaii birth certificates. Single live births to Hawaii-resident Samoan and Caucasian women from 1979 to 1994 were included in the study. Infants of Samoan women experienced a 75 g decline in mean birthweight and an increase in the percentage of low (< 2500 g) and very low (< 1500 g) birthweight from 2.6 and 0.4 to 3.8 and 0.8 respectively. During the same time, infants of Caucasian mothers experienced an increase in mean birthweight and a decline in low birthweight, while very low birthweight did not change. Maternal socio-demographic characteristics explained only part of the findings and use of prenatal care did not appear to be associated with any birth outcome indicators. Multiple regression analyses identified an adjusted loss of 50.8 g in birthweight and a 1.48 increase in the odds ratio of small-for-gestational-age associated with birth at the end (1991-4) compared with the beginning (1979-82) of the study period. Further studies focusing on maternal health status and psycho-social variables, including the effect of acculturation-related stress, are warranted to identify at least some of the determinants of the changes identified by this analysis.

Using national data, we develop and contrast the birth-weight percentiles for gestational age by infants of extremely-low-risk (ELR) White and African-American women and examine racial differences in the proportion of small-for-gestational-age (SGA) births. We then scrutinise racial variations in infant mortality rates of the infants of ELR women. We further compare the infant mortality rates of infants at or below the 10th percentile of birthweight for gestational age of each race group to determine whether infants with similar restricted fetal growth have comparable risks of subsequent mortality. Single live births, 34-42 weeks' gestation, to White and African-American US-resident mothers were selected from the 1990-91 US Linked Live Birth--Infant Death File (n = 4,360,829). Extremely-low-risk mothers were defined as: married, aged 20-34 years, 13+ years of education, multiparae, with average parity for age, adequate prenatal care, vaginal delivery, and no reports of medical risk factors, tobacco use or alcohol use during pregnancy. Marked racial variation in birthweight percentiles by gestational age was evident. Compared with ELR White mothers, the risk of an SGA infant was 2.64 times greater for ELR African-American mothers and the risk of infant mortality was 1.61 times greater. For the ELR group, the infant mortality rates of African-American and White infants at or below the 10th percentile of birthweight for gestational age of their respective maternal race group were essentially identical after controlling for gestational age. In conclusion, race differences in fetal growth patterns remained after controlling for risk status. Efforts to remove racial disparities in infant mortality will need to develop aetiological pathways that can explain why African-Americans have relatively higher rates of preterm birth and higher infant mortality rates among term and non-SGA infants.

The state of Hawaii has had near-universal health insurance coverage for the last 20 years. Its highly diverse population offers the opportunity for a unique, natural experiment in the United States on the examination of social differences in health care utilisation when financial barriers are removed. Therefore, the objective of this study is to examine predictors of prenatal care utilisation patterns in the four major ethnic groups in Hawaii. The data used in this study are the 1979-92 Hawaii livebirth vital record files. A total of 165,301 singleton livebirths to Hawaii-resident mothers of Caucasian, native Hawaiian, Japanese or Filipino ancestry were selected. Despite near-universal health care coverage in Hawaii, a surprising number of women did not adequately utilise prenatal care, with large differences between groups. Multivariate analyses indicated that similar maternal socio-demographic factors were associated with prenatal care use in each ethnic group. Social variation continues to exist among all ethnic groups even in the presence of universal access to care. These data emphasise the need to address the distinct cultural needs of populations for providing health services, and further challenge the assumption that removal of financial barriers will ensure a high level of prenatal care use.

This paper examines the utilization of prenatal care in Hawaii from 1979 to 1994 to determine if early and adequate utilization of prenatal care has changed during this period. Birth certificates of single live born infants of resident women were the source of data for the study. During the study period, the proportion of women receiving prenatal care in the first trimester increased by nearly 5 percent but was still below the national and state Year 2000 health objective of 90 percent. Notwithstanding this improvement, the percentage of women who did not receive the recommended number of visits in spite of starting care early significantly increased. The overall proportion of women with 'intensive' prenatal care use markedly increased (134.7%). The proportion of women with 'inadequate' care use declined (10.3%), although the proportion of women with 'no care' use doubled. Complete reporting of use of care through birth certificates markedly deteriorated. The findings of this study indicate the need for changes in the targeting and provision of counseling and education on the part of health care providers. Public health leaders, policy makers, health care providers, and advocacy groups need to collectively review programmatic directions with an aim toward the development of innovative approaches to address the emerging health needs of mothers and infants in the state.

This paper examines changes in maternal sociodemographic characteristics and pregnancy outcomes in Hawaii during the period 1979-1994. The more striking changes were increases of 129% in the proportion of births to women > 35 years old and of 67% in the proportion of births to unmarried mothers. The percentage of low birth weight and small-for-gestational age infants decreased while the proportion of premature births increased. Identified changes were not limited to selected population groups, but were found in various degrees in all ethnic groups. These findings are relevant to all health practitioners and will assist in the provision of appropriate care and counseling to individual women.

PURPOSE OF THE PAPER: This study provides baseline information on the characteristics of Native Hawaiian mothers and the health status of their infants, comparing residents of Hawaii with those of the continental U.S. The impact of Hawaii residence on low birth weight and infant mortality among Native Hawaiians is assessed. SUMMARY OF METHODS UTILIZED: Data from the National Center for Health Statistics 1983&shy;1987 Linked U.S. Live Birth and Infant Death file were used to examine parental characteristics, prenatal care use and infant outcomes using chi&shy;square and logistic regression procedures. PRINCIPAL FINDINGS: Despite a higher sociodemographic risk profile among Hawaii resident mothers, preterm birth, low and very low birth weight percentages were similar. Continental infants had significantly highter percentages of very pre&shy;term birth and macrosomia. Mortality rates in both the neonatal and post&shy;neonatal periods, and for SIDS and perinatal causes were elevated among continental infants. Hawaii residence had a borderline protective effect on infant mortality, wehn sociodemographic and prenatal care differences were controlled. CONCLUSIONS: This study suggests a possibly protective effect of Hawaii residence on the health of Native Hawaiian infants during the period of following employer&shy;mandated health insurance coverage but before the initiation of "gap&shy;group" coverage and the Native Hawaiian Health Care Systems in Hawaii. RELEVANCE TO ASIAN PACIFIC ISLANDER AMERICAN POPULATIONS. This is the first report documenting the sociodemographic and health status of the growing number of Native Hawaiian mothers and their infants residing outside of Hawaii. Expanded health insurance coverage and culturally appropriate and accessible health care may contribute to improved infant health status in Hawaii. Their absence, along with possible barriers of sociocultural isolation, may account for the poorer than expected outcomes of continental infants and predict a widening gap between them and their counterparts in Hawaii. A follow&shy;up study of the health status of Native Hawaiian mothers and infants, and their access to appropriate care in Hawaii and thei continental U.S. is recommended.

Percentages of low birth weight are low in American Indian and Mexican-American populations despite a high prevalence of traditional risk factors. Data derived from 1979-1990 Hawaii vital record files were used to examine birth weight, infant mortality, and their correlates in Samoan and Hawaiian residents of Hawaii to assess whether traditional risk factors are adequate predictors of low birth weight and whether low birth weight is an adequate measure of infant mortality risk in Polynesian populations. Despite very low educational attainment, high proportions of unmarried status, and inadequate prenatal care use, low and very low birth weight percentages were less than the US average. High birth weight was common. Unmarried status and primiparity after age 17 increased low birth weight risk, while high educational attainment and Samoan ethnicity decreased the risk. Adequate prenatal care was not associated with reduced low birth weight risk. Higher than expected neonatal mortality, particularly among normal birth weight infants, and high postneonatal mortality among Hawaiian infants suggest that poverty and maternal chronic disease, rather than low birth weight, may be the primary mediators of infant mortality risk in some populations. The need for clearer specification of risk factors and caution in generalized risk assessment in diverse populations is emphasized.

This study examines the association between maternal sociodemographic characteristics and the receipt of different levels of prenatal care use (no care, inadequate, intermediate, adequate) in order to determine different patterns in the relationships between maternal characteristics and these distinct categories of prenatal care use. Using the 1979-1992 Hawaii live birth vital record file, single live births to Hawaii resident mothers of white, Hawaiian/part-Hawaiian, Filipino, or Japanese ethnicity, who did not indicate on the birth certificate that either parent was active duty military, were selected. Over one quarter of this study population did not initiate prenatal care in the first trimester. Given the high level of insurance coverage found in Hawaii, this finding is disconcerting, particularly in relation to the U.S. Year 2000 Objective of 90% initiation in the first trimester. Overall, the factors that predicted receipt of any prenatal care predicted more adequate use of prenatal care as well. Noteworthy exceptions were maternal age and ethnicity. Identifying these exceptions is important for the development of a more detailed understanding of risk factors related to use of prenatal care to better target program responses aimed at improving prenatal care use. In addition, these data suggest that removing financial barriers to access to care does not guarantee universal use of disease prevention and health promotion services.

This study compares the maternal sociodemographic and prenatal care characteristics and birth outcomes of US resident white and Japanese-American mothers, using data from the state of Hawaii. The specific focus is to determine to what extent these factors can explain variations in newborn maturity and mortality indicators. Single livebirths to resident, non-military dependent white and Japanese-American mothers were selected for analysis from the 1979-1990 linked livebirth-infant death files from Hawaii. Compared with white mothers, Japanese-American mothers were significantly more likely to be married, age 18 years and older, have higher educational attainment, and have adequate prenatal care utilisation. The majority of Japanese-American mothers were born in Hawaii, while the majority of white mothers were born on the US mainland. The mean birthweight of Japanese-American infants was 200 g lighter than that of white infants. Infant mortality rates (IMRs) for both groups were below the US Year 2000 Health Objective. After controlling for maternal sociodemographic and prenatal care factors with logistic regression, Japanese-American infants had significantly higher risks of low birthweight, preterm and very preterm birth and of being small-for-gestational age. These findings indicate that populations with preferential maternal sociodemographic and prenatal care risk indicators may still exhibit higher low birthweight percentages, but achieve comparatively low IMRs.

Hawaii vital record data for 1979 through 1990 were analyzed to examine potentially differing relationships between maternal and infant risks and outcomes in native Hawaiian and White infants. Despite high rates of inadequate prenatal care and teenage and unmarried childbearing, the Hawaiian low-birth-weight rate was below the US average. Hawaiian infants experienced an elevated risk of mortality, particularly among those of normal birthweight during the postneonatal period. Public health initiatives to reduce infant mortality must go beyond preventing teenage pregnancy and low birthweight to address Hawaiian infants' unique pattern of risk factors and the social and economic environment in which such risks abound.

Objectives: We examined the pregnancy outcomes of three ethnic groups: African-American Blacks, non-Hispanic Whites, and Filipinos. In an attempt to reduce ethnic dissimilarities in parental employment and access to health care, this investigation compared the single-live-birth outcomes of married, adult women who resided in the state of Hawaii and who indicated that their spouse was on active-duty status in the US military., Methods: The data for this study were obtained from the 1979-1989 Hawaii vital-record file that provides linked live birth-infant death information. Multiple logistic regression was used to calculate odds ratios for the independent effects of maternal factors on low birthweight and neonatal mortality., Results: Significant differences in maternal age, maternal education, paternal education, parity, hospital of delivery, and use of prenatal care were observed among the ethnic groups. The results of a logistic regression analysis of low birthweight indicated significantly higher risks for Filipinos and Blacks compared with Whites. For very low birthweight, only an increased risk for Blacks was observed. No ethnic differences in neonatal mortality were found., Conclusions: This investigation revealed more comparable infant mortality experiences among the ethnic groups in spite of persistent birthweight differences.

Since the end of the Korean War, immigration of Koreans to the United States has increased rapidly. In 1990, 11.6 percent of all Asians in the United States were of Korean ethnicity, and it is projected that Koreans will outnumber all other Asian groups, except Filipinos, in the United States by the year 2030. Despite the growing size of this population, very little is known about their health status. This study, using 1979-89 Hawaii vital record data, investigates the relationship between maternal sociodemographic characteristics, prenatal care utilization factors, and birth outcomes among Koreans as compared with Caucasians. The ethnic term "Caucasian" is used in Hawaii's vital records and is synonymous with non-Hispanic whites. Korean mothers were more likely to be older and have lower educational attainment, and less likely to be adolescent, single, or to have received adequate prenatal care than Caucasian mothers. More than 80 percent of the Korean mothers were foreign born. Significantly higher risks for very preterm delivery (less than 33 weeks) and very low birth weight births were observed for Koreans as compared with Caucasians. Nativity had no effect on birth outcome in this population. The results of this study suggest that prevention of preterm birth is an important focus for improving pregnancy outcomes in this growing ethnic group.

Evidence from the Philippines suggests that, compared to Whites, infants born to Filipino women are more likely to be low birth weight. A paucity of information is available regarding birth outcomes of U.S.-born Filipinos. Using 1979-1987 Hawaii vital record data on single live births to resident mothers, this study compares the maternal characteristics and pregnancy outcomes of White and Filipino mothers, Filipino mothers were significantly more likely to be <18 years of age and single, and have lower educational attainment and less adequate utilization of prenatal care. Significantly higher percentages of very preterm, preterm, very low birth weight, low birth weight, and small for gestational age infants were found for Filipinos. The birth weight-specific neonatal mortality rates for Filipinos compared favorably to Whites except at the high end of the birth weight distribution. After taking into account maternal sociodemographic risk and prenatal care factors in a logistic regression, a significant ethnic difference in low birth weight persisted but was not found for neonatal mortality. These data may suggest that similar neonatal mortality rates among ethnic groups may be possible in the face of persistent birth weight distribution differences and add to the growing evidence that a single standard of low birth weight may be inappropriate as an universal indicator of health status risk in a multi-ethnic population. © 1993 Wiley-Liss, Inc., (Copyright © 1993 Wiley-Liss, Inc., A Wiley Company.)