Testicular tissue cryopreservation: 8 years of experience from a coordinated network of academic centers.

STUDY QUESTION: Is it feasible to disseminate testicular tissue cryopreservation with a standardized protocol through a coordinated network of centers and provide centralized processing/freezing for centers that do not have those capabilities? SUMMARY ANSWER: Centralized processing and freezing of testicular tissue from multiple sites is feasible and accelerates recruitment, providing the statistical power to make inferences that may inform fertility preservation practice. WHAT IS KNOWN ALREADY: Several centers in the USA and abroad are preserving testicular biopsies for patients who cannot preserve sperm in anticipation that cell- or tissue-based therapies can be used in the future to generate sperm and offspring. STUDY DESIGN, SIZE, DURATION: Testicular tissue samples from 189 patients were cryopreserved between January 2011 and November 2018. Medical diagnosis, previous chemotherapy exposure, tissue weight, and presence of germ cells were recorded. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human testicular tissue samples were obtained from patients undergoing treatments likely to cause infertility. Twenty five percent of the patient's tissue was donated to research and 75% was stored for patient's future use. The tissue was weighed, and research tissue was fixed for histological analysis with Periodic acid-Schiff hematoxylin staining and/or immunofluorescence staining for DEAD-box helicase 4, and/or undifferentiated embryonic cell transcription factor 1. MAIN RESULTS AND THE ROLE OF CHANCE: The average age of fertility preservation patients was 7.9 (SD = 5) years and ranged from 5 months to 34 years. The average amount of tissue collected was 411.3 (SD = 837.3) mg and ranged from 14.4 mg-6880.2 mg. Malignancies (n = 118) were the most common indication for testicular tissue freezing, followed by blood disorders (n = 45) and other conditions (n = 26). Thirty nine percent (n = 74) of patients had initiated their chemotherapy prior to undergoing testicular biopsy. Of the 189 patients recruited to date, 137 have been analyzed for the presence of germ cells and germ cells were confirmed in 132. LIMITATIONS, REASONS FOR CAUTION: This is a descriptive study of testicular tissues obtained from patients who were at risk of infertility. The function of spermatogonia in those biopsies could not be tested by transplantation due limited sample size. WIDER IMPLICATIONS OF THE FINDINGS: Patients and/or guardians are willing to pursue an experimental fertility preservation procedure when no alternatives are available. Our coordinated network of centers found that many patients request fertility preservation after initiating gonadotoxic therapies. This study demonstrates that undifferentiated stem and progenitor spermatogonia may be recovered from the testicular tissues of patients who are in the early stages of their treatment and have not yet received an ablative dose of therapy. The function of those spermatogonia was not tested. STUDY FUNDING/COMPETING INTEREST(S): Support for the research was from the Eunice Kennedy Shriver National Institute for Child Health and Human Development grants HD061289 and HD092084, the Scaife Foundation, the Richard King Mellon Foundation, the Departments of Ob/Gyn & Reproductive Sciences and Urology of the University of Pittsburgh Medical Center, United States-Israel Binational Science Foundation (BSF), and the Kahn Foundation. The authors declare that they do not have competing financial interests.

[Three horizontal muscle surgery for infantile esotropia and decompensated microtropia]. / Horizontale Dreimuskelchirurgie bei frühkindlichem Innenschielen und dekompensiertem Mikrostrabismus.

BACKGROUND: Surgical management of large-angle infantile esotropia and decompensated microtropia has been controversially debated. There seems to be a relative bias against surgery on more than two horizontal muscles to avoid overcorrections. In our study we report on the sensory and motor outcomes after three horizontal muscle surgery. Furthermore we aim to suggest a table to guide surgery amounts. PATIENTS AND METHODS: This study was a retrospective interventional cohort of 27 patients (16 female, 11 male; mean age 7.9 [years], ranging from 1 to 27 [years]) with infantile esotropia and decompensated microtropia who underwent three horizontal muscle surgery (bilateral medial rectus muscle recession and lateral rectus muscle plication) between 2005 and 2013. RESULTS: Preoperative deviation in primary position measured 30.2 [°] (mean; range 21.9 to 48.0). Postoperatively esotropia was significantly reduced to 2.6 [°] (mean; range -16.7 to 16.7). After six months deviation measured 5.5 [°] (mean, range -14.1 to 21.9). An effect of 1.63°/mm was calculated for the combined three muscle surgery. CONCLUSIONS: For the correction of large-angle infantile esotropia and decompensated microtropia three horizontal muscle surgery is associated with a high success rate. Only a very low rate of consecutive exotropia does occur.

Early onset of acquired comitant non-accommodative esotropia in childhood.

BACKGROUND: The aim of this study was to describe the clinical characteristics and surgical outcome of acquired comitant non-accommodative esotropia without obvious cause in children with an early onset ≤ three years of age. PATIENTS AND METHODS: 24 consecutive patients (13 females) with acquired comitant non-accommodative esotropia underwent strabismus surgery. Outcome measures included amount of deviation and level of binocularity at last follow-up. RESULTS: An acute onset of strabismus was observed in 83 % of patients. Accompanying features such as diplopia, covering one eye or stumbling were observed in 40 % of the children. Cycloplegic retinoscopy revealed a mild to moderate hypermetropia in all children (mean hypermetropia + 2.2 diopters). 90.5 % of children were aligned within 8 PD of orthotropia. 81 % regained normal stereovision (Lang I/II). CONCLUSIONS: All children exhibited the typical features of acute acquired comitant esotropia (AACE) type II (Burian-Franceschetti). Collective characteristics of this form of strabismus are a comitant and relatively large deviation, mild hypermetropia, a potential of normal binocular cooperation and absence of an accommodative component and neurological pathology. Time and suddenness of strabismus onset may be less helpful in defining this entity.

[Diagnosis and treatment of oculomotor deficits in Möbius sequence]. / Diagnose und Therapie okulomotorischer Defizite bei Patienten mit Möbius-Sequenz.

This article reviews the spectrum of possible motility disorders and ocular misalignment in patients with Möbius sequence. The various options for strabismus surgery are discussed and a stepwise algorithm is presented.

[Non-oculomotor eye involvement in Moebius sequence]. / Nichtokulomotorische Augenbeteiligung bei Möbius-Sequenz.

Moebius sequence is a congenital disorder that not only affects the oculomotor system but also the eyes themselves. Ocular involvement might be sight-threatening and needs regular follow-up by an ophthalmologist.

Ophthalmological findings in Joubert syndrome.

PURPOSE: Joubert syndrome (JS) is an autosomal-recessive inherited complex malformation of the midbrain-hindbrain. It has been associated with ocular and oculomotor abnormalities. The aim of our study was to extend the ophthalmic knowledge in JS and to add new findings. METHODS: In a retrospective study, 10 consecutive patients, who met the revised diagnostic criteria of JS were included. Mutation analysis was carried out in all the cases. Each patient underwent a comprehensive neuro-ophthalmological examination. RESULTS: Bilateral drusen of the optic disc were found in two patients. Four patients showed bilateral morphological and functional signs of retinal dystrophy (CEP290 mutation in two cases and AHI1 mutation in one case). In nine patients performance during smooth pursuit, saccades, and vestibulo-ocular reflex (VOR) cancellation was poor. CONCLUSIONS: To the best of our knowledge, the association of optic disc drusen with JS has not yet been described. In support of the earlier findings, decreased smooth pursuit and VOR cancellation, as well as partial-to-complete oculomotor apraxia seem to be the key oculomotor features of JS. Genotype-phenotype correlations showed the predictive value of CEP290 and AHI1 mutations for retinal involvement.

Rare retinal haemorrhages in translational accidental head trauma in children.

PURPOSE: The characteristic findings in accidental head injury consist of linear skull fracture, epidural haematoma, localized subdural haematoma, or cortical contusion because of a linear or translational impact force. Retinal haemorrhages have been found, although uncommon, in accidental head trauma. METHODS: We performed a retrospective study of 24 consecutive cases of children with severe head injuries caused by falls. Inclusion criteria were skull fractures and/or intracranial haemorrhages documented by computerized tomography. All patients underwent a careful ophthalmic examination including dilated indirect fundoscopy within the first 48 h following admission. RESULTS: No retinal haemorrhages could be found in patients whose accidents were plausible and physical and imaging findings were compatible with reported histories. Excessive bilateral retinal haemorrhages were found in only three children with the typical signs of shaken baby syndrome. In eight children, trauma had led to orbital roof fractures. CONCLUSIONS: Retinal haemorrhages were not found in any of the patients with accidental trauma despite the severity of their head injuries. Hence, we add more evidence that there are strong differences between the ocular involvement in accidental translational trauma and those in victims of non-accidental trauma. Fall-related injuries carry a very low risk of retinal haemorrhages.

Features of age-related macular degeneration assessed with three-dimensional Fourier-domain optical coherence tomography.

BACKGROUND/AIMS: Age-related macular degeneration (AMD) is among the leading causes of severe visual loss in individuals over 60 years old. Retinal changes associated with AMD were previously studied by time-domain optical coherence tomography (OCT). Recently, Fourier-domain OCT (FD-OCT) has been introduced. FD-OCT provides increased scan resolution and scanning speed, and generates three-dimensional (3D) OCT images. The purpose of this study was to demonstrate features of AMD assessed with high-density scanning 3D-FD-OCT (Topcon 3D-OCT1000). METHODS: The study was designed as a prospective, observational case series. Five patients with typical morphological changes due to AMD were chosen based on funduscopic findings. Eyes with non-exudative- and exudative AMD were included. 3D-FD-OCT images were obtained, and typical morphological changes associated with AMD were presented. RESULTS: FD-OCT provided detailed 3D-images of retinal structure. In addition, FD-OCT showed improved retinal coverage and image quality. FD-OCT B-scan imaging identified typical retinal changes associated with AMD. In addition, FD-OCT imaging revealed information about the extent and the 3D shape of retinal lesions. CONCLUSION: 3D-FD-OCT imaging is useful for diagnosing and following patients with AMD. In addition, 3D-FD-OCT provided information about the extent and 3D shape of retinal pathologies and showed improved retinal coverage.

Retinal haemodynamics in patients with age-related macular degeneration.

OBJECTIVE: To investigate whether there is an association between the magnitude of retinal haemodynamic abnormalities in patients with age-related macular degeneration (AMD) and the degree of severity of the AMD. METHODS: A retinal laser Doppler system (Canon CLBF 100) was used to measure retinal arterial haemodynamic parameters in 25 eyes of 25 patients with AMD and nine eyes of nine age-matched control subjects. Severity of AMD was classified into Mild (n=11), Moderate (n=7), or Severe (n=7). The pulsatility ratio (PR), the pulsatility index (PI), and the resistivity index (RI) were determined. RESULTS: PR, PI, and RI in the patients with AMD were each significantly higher than in the control group, and increased monotonically with increasing severity of AMD. However, there were no differences in mean blood velocity, arterial diameter, or blood flow rate among the groups. This suggests that the increased blood flow pulsatility in the retinal arteries of the eyes with AMD is not due to increased distal vascular resistance, but instead is likely due to a loss of compliance in the arterial vasculature leading to the eye. CONCLUSION: Our results suggest that an increasing vascular rigidity in the systemic arterial circulation is directly associated with an increasing severity of AMD.