[Surgical Methods in the Treatment of Uveal Melanoma]. / Chirurgische Methoden in der Behandlung des Aderhautmelanoms.

Significant advancements have been made in the last decades in the treatment of uveal melanoma. Radiation therapy can achieve, depending on the method, local tumour control in up to 98% of cases. Surgical modalities have been implemented in the ocular therapy for uveal melanoma either to treat/prevent radiation complications, such as so-called toxic tumour syndrome, or to primarily treat the tumour with or without adjunctive radiotherapy. These include endoresection and transscleral resection for melanomas of the choroid/ciliary body or irido-trabeculo-cyclectomy for melanomas of the iris-ciliary body. Furthermore, tumour biopsy is playing a progressively more important role in the diagnosis, treatment and follow-up planning of melanoma cases. This paper focuses on the background, the surgical technique as well as the results and complications of tumour excisional and biopsy surgery.

Double Reverse Overlapping Scleral Trapdoor (DROST) Technique for the Removal of Juxtalenticular Intraocular Foreign Body.

We describe the double reverse overlapping scleral trapdoor (DROST) technique, a novel minimally invasive technique for the removal of very anterior intraocular foreign bodies without the need of pars plana vitrectomy. [Ophthalmic Surg Lasers Imaging Retina 2023;54:600-602.].

Two Cases of Acute Macular Neuroretinopathy Associated with the Adenovirus-based COVID-19 Vaccine Vaxzevria (Astrazeneca).

PURPOSE: To report two cases of acute macular neuroretinopathy (AMN) in young female patients following the administration of the adenovirus-based coronavirus disease 2019 (COVID-19) vaccine Vaxzevria (AstraZeneca). METHODS: Spectral-domain optical coherence tomography and infrared imaging were used to confirm the diagnosis of AMN. RESULTS: Both patients showed a parafoveal hyperreflective band in the outer nuclear layer, disruption of the ellipsoid and interdigitation zones of the photoreceptor layers, and correlating hyporeflective areas on the near-infrared images. Both patients presented with flu-like fever and sudden onset of fortifications within 48 hours of vaccination. One patient showed altered flow in the deep capillary plexus and highly elevated thrombotic parameters. CONCLUSION: We report a possible association between immune-mediated AMN and the administration of adenovirus-based COVID-19 vaccine Vaxzevria.

Serpinin in the Skin.

The serpinins are relatively novel peptides generated by proteolytic processing of chromogranin A and they are comprised of free serpinin, serpinin-RRG and pGlu-serpinin. In this study, the presence and source of these peptides were studied in the skin. By Western blot analysis, a 40 kDa and a 50 kDa protein containing the sequence of serpinin were detected in the trigeminal ganglion and dorsal root ganglia in rats but none in the skin. RP-HPLC followed by EIA revealed that the three serpinins are present in similar, moderate amounts in rat dorsal root ganglia, whereas in the rat skin, free serpinin represents the predominant molecular form. There were abundant serpinin-positive cells in rat dorsal root ganglia and colocalization with substance P was evident. However, much more widespread distribution of the serpinins was found in dorsal root ganglia when compared with substance P. In the skin, serpinin immunoreactivity was found in sensory nerves and showed colocalization with substance P; as well, some was present in autonomic nerves. Thus, although not exclusively, there is evidence that serpinin is a constituent of the sensory innervation of the skin. The serpinins are biologically highly active and might therefore be of functional significance in the skin.

Characteristic facial features and cortical blindness distinguish the DOCK7-related epileptic encephalopathy.

BACKGROUND: The epileptic encephalopathies display extensive locus and allelic heterogeneity. Biallelic truncating DOCK7 variants were recently reported in five children with early-onset epilepsy, intellectual disability, and cortical blindness, indicating that DOCK7 deficiency causes a specific type of epileptic encephalopathy. METHODS: We identified 23- and 27-year-old siblings with the clinical pattern reported for DOCK7 deficiency, and conducted genome-wide linkage analysis and WES. The consequences of a DOCK7 variant were analyzed on the transcript and protein level in patients' fibroblasts. RESULTS: We identified a novel homozygous DOCK7 frameshift variant, an intragenic tandem duplication of 124-kb, previously missed by CGH array, in adult patients. Patients display atrophy in the occipital lobe and pontine hypoplasia with marked pontobulbar sulcus, and focal atrophy of occasional cerebellar folia is a novel finding. Recognizable dysmorphic features include normo-brachycephaly, narrow forehead, low anterior and posterior hairlines, prominent ears, full cheeks, and long eyelashes. Our patients function on the level of 4-year-old children, never showed signs of regression, and seizures are largely controlled with multi-pharmacotherapy. Studies of patients' fibroblasts showed nonsense-mediated RNA decay and lack of DOCK7 protein. CONCLUSION: DOCK7 deficiency causes a definable clinical entity, a recognizable type of epileptic encephalopathy.

Proton beam radiation for iris melanoma: case series and review of literature.

OBJECTIVE: Purpose of this study is to analyse the visual outcomes, the complication and eye retention rate as well as tumour control data of patients treated with proton beam radiation therapy (PBRT) for iris melanoma. METHODS: Retrospective case series and review based on patients' records. All tumours were categorised according to the American Joint Committee of Cancer staging criteria for primary iris melanoma und underwent either sectorial or whole anterior segment PBRT. RESULTS: Thirteen cases were identified of which five received PBRT of the whole anterior segment and eight received sectorial PBRT. Local tumour control after a mean follow-up of 25 months was 92%. Complications after PBRT included cataract (46%), secondary glaucoma (31%), superficial keratitis (15%) and madarosis (8%). Complications were more common in patients necessitating irradiation of the entire anterior segment than in patients which received sectorial irradiation. Eye retention was achieved in all cases. No statistically significant difference in the mean best corrected visual acuity (BCVA) and intraocular pressure (IOP) was found before and after treatment. Comparison of mean BCVA and IOP between different treatment groups (complete anterior segment vs sectorial irradiation) at the last follow-up visit were also not significantly different. No patient developed metastatic disease during follow-up. CONCLUSION: PBRT is a safe and vision preserving therapeutic modality for iris melanoma. Complete irradiation of the anterior segment is associated with higher complication rates.

Ultra-wide-field imaging of choroidal melanoma before and after proton beam radiation therapy.

OBJECTIVE: To evaluate the imaging characteristics of choroidal melanoma before and after proton beam radiotherapy via Optos® ultra-wide-field scanning laser ophthalmoscopy. METHODS: Retrospective, descriptive study of choroidal melanoma patients treated with proton beam radiotherapy. All patients underwent full clinical evaluation, including best-corrected visual acuity, ultrasound examination and ultra-wide-field scanning laser ophthalmoscopy imaging in the pseudo-colour (red and green channel) as well as auto-fluorescence mode. Tumours were classified and evaluated according to their location, size, presence of subretinal fluid, drusen, orange pigment and reflectance intensity in ultra-wide-field scanning laser ophthalmoscopy. Tumour sonographic (basal diameter, height) and ultra-wide-field scanning laser ophthalmoscopy imaging dimensions (maximal diameter) were documented. RESULTS: A total of 39 eyes (38 patients) were followed for 24 months (range 6-48 months). Mean best-corrected visual acuity dropped from 20/40 to 20/63 after proton beam radiotherapy. There was no change in the imaging tumour characteristics during follow-up. Subretinal fluid changes were better detected in the autofluorescence compared to pseudo-colour mode. Mean tumour diameter did not significantly change in the ultra-wide-field scanning laser ophthalmoscopy although it did so in the ultrasound. No patient showed local tumour recurrence. CONCLUSION: The ultra-wide-field scanning laser ophthalmoscopy imaging characteristics of choroidal melanoma in the Optos® system do not significantly change after proton beam radiotherapy after a mean follow-up of 2 years.

C-Shaped Scotoma after Complicated Cesarean Section: A Case of Acute Macular Neuroretinopathy.

Acute macular neuroretinopathy (AMN) is a rare retinal disease that produces transient or permanent visual impairment and occurs predominantly in young, Caucasian women of childbearing age. It is often characterized by wedge-like macular lesions. Although the cause of AMN is unknown, recent research suggests a microvascular etiology. Various vascular pathologies, including post-viral illness, oral contraceptives, and use of vasoconstrictive agents, have been associated with AMN. We present a case of a woman with C-shaped visual field defects in both eyes after inadvertent exposure to intravenous high-dose epinephrine during onset of spinal anesthesia. At present, only 8 cases of AMN after exposure to epinephrine have been described in literature. To our knowledge, this is the first case of AMN that presented following epinephrine injection during childbirth.

Early electroretinographic features of streptozotocin-induced diabetic retinopathy.

BACKGROUND: This study set out to document the early electrophysiological and immunohistochemical changes that occur in the retina of experimentally induced diabetic rats. METHODS: Diabetes was induced in rats by intraperitoneal injection of 60 mg/kg of streptozotocin (STZ). Electroretinogram readings were taken monthly under either short-duration or long-duration stimuli for up to 3 months after STZ. Oscillatory potentials (OP) and the amplitudes and implicit times of a- and b-waves were analysed, and b-wave amplitudes were analysed using a Naka-Rushton fit. Scotopic a-waves were analysed with photoreceptor models, and Rmp3 (the maximum a-wave amplitude) and S (sensitivity) were calculated. Three months after STZ injection, immunohistochemistry for glial fibrillary acidic protein was performed on the retinas of the STZ-treated rats and age-matched controls. RESULTS: The implicit OP times were significantly longer in the diabetic rats as compared with the controls, and this difference was noted as early as 1 month following STZ treatment. Other electrophysiological parameters, such as OP amplitudes, a- and b-wave amplitude as well as the implicit times, did not differ from controls at this stage. The sacrificed STZ-treated rats also demonstrated marked enhancement of glial fibrillary acidic protein immunoreactivity, suggesting that at least in experimentally induced diabetic retinopathy there is increased Müller cell reactivity. CONCLUSION: The results of this study indicated that functional alterations in the retina develop rapidly after the onset of diabetes. Analysis of each electroretinogram component may be useful in further investigating the development mechanisms of diabetic retinopathy.

Scotopic threshold responses to infrared irradiation in cats.

Infrared (IR) irradiation is frequently used in ophthalmological diagnosis and treatment. It has been used to selectively stimulate photodiode-based retinal prostheses to prove their function. Data concerning the natural IR-sensitivity of the retina are contradictory. In our experiments in dark-adapted cats an IR-laser (826 nm) and IR emitting diodes (875 nm) elicited clear scotopic threshold responses. Comparison of the two lasers (IR and a visible laser at 670 nm) using Lambs template and our experimental data revealed very similar differences in retinal sensitivity (4.28 and 3.94+/-0.29 log units, respectively). The fact that the cat retina is sensitive to IR-irradiation under certain conditions has important implications in interpreting the results from retinal prostheses and rewards further attention in its use in many ophthalmological applications.

Ocular trauma in a Greek population: review of 899 cases resulting in hospitalization.

PURPOSE: To determine the annual hospitalization rate and risk factors of eye injuries requiring hospitalization in an area of Greece. METHODS: Retrospective case analysis of 899 consecutive patients with ocular injury admitted at the Department of Ophthalmology, University Hospital at Patras Medical School, Greece, over a 9-year period. RESULTS: The average annual rate of hospitalized ocular injuries was 71.0 eye injuries per 1000 admissions at the Department of Ophthalmology. The majority (80.2%) of patients were male. The average age was 35.0 years (range 6 months-98 years). Approximately half of all injuries occurred in persons younger than 29 years of age. Patients with Albanian ethnic background were at higher risk. The most common type of injury was closed-globe injury (49.5%) that affected more frequently the very young individuals (0-19 years) and persons older than 50 years of age. Open-globe injuries occurred most often in young adults, 20 to 39 years of age, and comprised over 35% of all eye injuries in this age group. Most injuries (32.8%) occurred at the workplace, most commonly during construction activities. Injuries at home approximated the work-related injuries (30.0%). A total of 398 (42.5%) eyes underwent surgical intervention on the eye globe, while 49 (12.3%) of them underwent multiple operations as part of their treatment. 18.2% of the eyes were blinded and 27.9% had significant visual acuity loss. An enucleation during the follow-up period was performed in 4 (1.0%) eyes. CONCLUSIONS: Trauma is an important cause of ocular morbidity in Greece. Risk factors include young age, male gender, Albanian ethnic background, and workplace. General safety precautions and behavior modification are indicated.

Toxicity study of erucylphosphocholine in a rat model.

PURPOSE: To investigate the effect of intraocular erucylphosphocholine (ErPC) on the retina, the retinal pigment epithelium (RPE), and the choroid in an in vivo rat model. METHODS: Adult male Brown Norway rats were injected intravitreally with ErPC dissolved in balanced salt solution (BSS) at a final concentration of 10 or 100 microM with BSS serving as control. Adverse effects on the anterior and posterior segment were assessed by slit-lamp biomicroscopy and ophthalmoscopy. Retinal toxicity was assessed by electroretinography (ERG), retinal ganglion cell (RGC) quantification, and histology 7 days after intravitreal administration of ErPC. RESULTS: There was neither a statistically significant difference in the clinical examination nor in the ERG waves of treated versus control rats 7 days after intravitreal administration of ErPC. Correspondingly, the number of RGC after BSS injection did not differ significantly from ErPC-injected animals. Histologic sections of the posterior segment of 10 and 100 microM ErPC-injected rats did not show any signs of retinal toxicity. Electron microscopy did not display a difference between the 10 microM and the control group. Only the 100 microM-injected animals showed a discrete irregularity of the Müller cell and the retinal ganglion cell cytoplasm at the ultrastructural level. CONCLUSIONS: ErPC can safely be injected into the vitreous of adult rats at a concentration of 10 microM without any retinal toxicity. Even a 10-fold increase in ErPC concentration leads only to a discrete cytoplasmic irregularity of the innermost retinal layers.

Repeated transchoroidal implantation and explantation of compound subretinal prostheses: an exploratory study in rabbits.

PURPOSE: For human trials with retinal prostheses it is mandatory to develop procedures to safely explant and possibly reimplant the devices. This prompted us to investigate in a small exploratory study the safety of repeated transchoroidal implantation and explantation procedures of complex subretinal devices in laboratory animals. METHODS: Repeated transchoroidal surgery was performed in four rabbits. The rabbits were examined by clinical examination and funduscopy. Function was assessed by electroretinography and cortical recordings following light and subretinal electrical stimulation. Sections of the retina and of the implantation channel were examined by light microscopy. RESULTS: Using the same access route, repeated transchoroidal subretinal implantation surgery was successfully performed in all cases. Fixation of implants was stable for up to 13 months; retinas remained attached at all examination dates. Electroretinograms and visual evoked cortical potential proved retinal and visual pathway integrity. Subretinal electrical stimulation elicited retinal and cortical responses. While retinal morphology at earlier stages was found to be essentially unaltered, atrophic disorganization in the region of the subretinal channel was observed after 10 months and after subretinal electrical stimulation. CONCLUSIONS: Repeated transchoroidal surgery can be safely performed for implantation, explantation, and reimplantation of subretinal devices in rabbits. With modifications, we believe the technique can be applied in human surgery.

Investigation of thermal effects of infrared lasers on the rabbit retina: a study in the course of development of an active subretinal prosthesis.

BACKGROUND: Retinal implants are intended to replace photoreceptors in patients suffering from degenerative retinal diseases such as retinitis pigmentosa. Data show that photodiodes in subretinal implants are not powerful enough to stimulate overlying retinal tissue by simply transforming light energy into electrical energy. Therefore, infrared (IR) irradiation has been envisioned to supply additional energy. While epiretinal implants mostly use induction coils for wireless energy transfer, IR irradiation seems to be an additional option. This study investigated the feasibility of an IR energy supply for an active subretinal implant by assessing thermal effects of IR irradiation onto the rabbit retina. METHODS: Polyimide foil strips carrying an optical sensor as well as a thermal sensor were implanted into the subretinal space of the eyes of nine rabbits using a transchoroidal surgical approach. The area of the thermal sensor was irradiated by an IR laser (830 nm) focused on the device. The sensor provided simultaneous real-time measurements of absolute temperature and irradiation density, allowing direct correlation of the temperature increase to different intensities of IR irradiation. Possible IR-related damage to the retina was examined in histological sections. Temperature changes in living and dead animals were evaluated as a function of IR irradiation power of between 0.1 mW and 40 mW (0.03 mW/mm2-12.7 mW/mm2). RESULTS: We found an exponential relationship between IR irradiation power and temperature increase over the whole range (up to 12.7 mW/mm2) in the living animal. The maximum temperature increase caused by IR irradiation of 40 mW (12.7 mW/mm2) was 4.5 degrees C. The ratio of temperature increase to IR irradiation density postmortem (i.e., without ocular blood flow) was linear over the whole range, with 1.15 degrees C per 1 mW/mm2. Thus, the cooling effect of ocular blood flow varied depending on IR irradiance density. In histological sections, no IR-induced damage to the retina was detected. CONCLUSIONS: A temperature increase of 3.2 degrees C in the living rabbit eye is to be expected when powering a subretinal implant with 15 mW (4.8 mW/mm2) IR power, the wattage used in an external power supply for an active implant with 1,500 electrodes. This appears to be a tolerable increase for ocular tissue.

Retinal neurodegeneration in the DBA/2J mouse-a model for ocular hypertension.

Mice of the DBA/2J strain spontaneously develop complex ocular abnormalities, including glaucomatous loss of retinal ganglion cells (RGC). In the present study ultrastructural features of retinal neurodegeneration in DBA/2J mice of different age (3, 6, 8 and 11 months) are described. By 3 months, RGC apoptosis characterized by electron-dense karioplasm and cytoplasm of ganglion cells was observed. The occurrence of apoptotic ganglion cells peaked at the age of 6 months. Past this age, necrosis characterized by swelling and electron-rare cytoplasm appeared to be the prevailing form of cell death. Müller glia activation increased with age, but there were no signs of leukocyte infiltration. At 8 and 11 months, signs of neoangiogenesis were found both at the ultrastructural level and in clinical examinations. In these older animals myelin-like bodies, most probably representing the intracellular aggregates of phospholipids in irreversibly injured cells, were also seen. Photoreceptor cells were not affected at any age. Our observations suggest that retinal degeneration in the DBA/2J mice does not involve recruitment of blood-borne inflammatory/phagocytosing cells, and that apoptosis is gradually replaced by necrosis as the predominant pathway of RGC death. Retinal degeneration in 3- to 11-month-old DBA/2J mice partially resembles human pigment dispersion syndrome and pigmentary glaucoma with characteristic anterior segment changes and elevation of intraocular pressure. However, neovasculogenesis and myelin-like bodies are observed during aging. Therefore, the DBA/2J model requires judicious interpretation as a glaucoma model.