Unusual anterior and posterior segment features of coats disease.

PURPOSE: To report the clinical course and management of unusual anterior and posterior segment features of Coats disease and their relation to the age of the patients to increase the awareness towards these rare clinical features rarely described in the current literature. METHODS: A retrospective descriptive review of 45 eyes of 45 patients affected by Coats disease was conducted at the Retinoblastoma Referral Center and Ophthalmology Unit of the University of Siena in Italy analyzing data from 2000 to 2022. Medical records and images were revised to find some cases presenting unusual anterior and posterior segment features in patients affected by Coats disease.We identified therefore 4 unusual clinical conditions: retinal macrocysts, anterior chamber cholesterolosis, fovea-sparing Coats disease and secondary vasoproliferative tumor. RESULTS: Two patients presented with retinal macrocyst (2/45 = 4.4%), one with anterior chamber cholesterolosis (1/45 = 2.2%), two with fovea sparing Coats disease (2/45 = 4.4%) and one with vasoproliferative tumor associated (1/45 = 2.2%) for a total of six (6/45 = 13.3%) patients manifesting unusual anterior or posterior segment features in Coats disease. CONCLUSION: Unusual anterior and posterior segment features of Coats disease such as retinal macrocyst and anterior chamber cholesterolosis have been more frequently reported in younger children while fovea-sparing and vasoproliferative tumors have been more commonly described in older patients. Age is then a strong prognostic marker which allows to distinguish two different phenotypes of Coats disease: patients younger and older than 3 years old with more aggressive and milder phenotype respectively.

Medulloepithelioma in newborn: Advanced clinical status.

We report three cases of congenital medulloepithelioma, which is an extremely rare clinical pattern of a tumor rare by definition. The aim of this study is to underline the clinical features of advanced medulloepithelioma in newborns.

Very late orbital recurrence of choroidal melanoma four decades post enucleation.

Orbital recurrence of malignant choroidal melanoma is quite uncommon, occurring in about 3% of patients undergoing enucleation for large tumors. Orbital recurrences after more than 10 years from enucleation are even rarer. In literature, only few reports described orbital recurrence that occurred between 10 and 40 years after primary diagnosis. Herein we report a very late choroidal melanoma recurrence, 40 years post enucleation, of a 52 year-old female who had undergone left enucleation at the age of 12. She presented to our clinic for consultation in 2017, complaining of difficulty to contain the prosthesis, as well as, presence of small pigmented palpable nodules inferiorly in her anophthalmic socket. The patient was not aware of the medical condition which had lead to the enucleation. We requested her medical reports and detailed history through her family. We realized after reviewing her charts 40 years back, that her enucleation was due to malignant choroidal melanoma (CMM). Full screening was performed. After magnetic resonance imaging (MRI), that showed the presence of nodular masses in the anophthalmic socket, an excisional biopsy was performed. Histopathology confirmed the diagnosis of CMM (epithelioid and spindle cell type), supporting the hypothesis that residual melanoma cells may remain clinically dormant for long periods, even for decades. A literature review was performed in order to review similar cases and to understand and discuss multiple factors, which may explain this extremely delayed recurrence. To the best of our knowledge, this is the third case to be reported in the literature.

Fovea-sparing coats disease: A rare clinical entity.

PURPOSE: To evaluate the rarity, clinical features and management of Coats disease characterized by fovea-sparing enhancing the importance of pediatric retinal screening and early management to maintain a good visual acuity. METHODS: Retrospective analysis of approximately 40 patients affected by Coats disease between 2000 and 2020 at the Retinoblastoma Referral Center and Ophthalmology unit of the University of Siena in Italy. RESULTS: Two patients with fovea sparing Coats disease were included. Both presented an extrafoveal Coats disease (stage 2A by Shields classification) when they were 5 and 6 years old respectively.They had no anterior findings and a presenting visual acuity of 20/20 reflecting the early stage and a milder phenotype of the disease which are indeed more likely to be found in patients older than 3 years at presentation.Both presented telangiectasia and retinal exudation in the affected eye. Standard Argon laser photocoagulation and subsequently Cryotherapy were performed in the telangiectatic retinal periphery of both patients obtaining an excellent control and regression of the disease. CONCLUSIONS: Careful pediatric retinal screening and early management are crucial to ensure a good visual prognosis in such an early feature of Coats disease as fovea sparing since this condition unfortunately tends to recall the physician's attention in more advanced stages.Due to the extremely poor number of articles regarding such a rare feature of Coats disease like fovea sparing, we report our experience.

The Second Division of Trigeminal Nerve for Corneal Neurotization: A Novel One-Stage Technique in Combination With Facial Reanimation.

Corneal neurotization represents an effective surgical strategy to restore corneal sensibility in patients affected by neurotrophic keratopathy.Corneal sensibility is essential in preserving structure and function of the eye. Loss of corneal sensibility can lead to a degenerative condition of the cornea known as neurotrophic keratopathy.Moreover, patients suffering from facial palsy show failure of full eyelid closure resulting in chronic corneal exposure and subsequent progressive damage.Reports have shown that the use of the contralateral ophthalmic division of the trigeminal nerve can be effective in restoring corneal sensibility. In the present study the authors expose a new technique by means of which direct neurotization of the anesthetic cornea was achieved using the homolateral second division of the trigeminal nerve. Effectiveness of the technique was evaluated using in vivo confocal microscopy.To the best of authors' knowledge, this is the first report of this technique in literature.

Blindness and Glaucoma: A Multicenter Data Review from 7 Academic Eye Clinics.

PURPOSE: To evaluate frequency, conversion rate, and risk factors for blindness in glaucoma patients treated in European Universities. METHODS: This multicenter retrospective study included 2402 consecutive patients with glaucoma in at least one eye. Medical charts were inspected and patients were divided into those blind and the remainder ('controls'). Blindness was defined as visual acuity≤0.05 and/or visual field loss to less than 10°. RESULTS: Unilateral and bilateral blindness were respectively 11.0% and 1.6% at the beginning, and 15.5% and 3.6% at the end of the observation period (7.5±5.5 years, range:1-25 years); conversion to blindness (at least unilateral) was 1.1%/year. 134 eyes (97 patients) developed blindness by POAG during the study. At the first access to study centre, they had mean deviation (MD) of -17.1±8.3 dB and treated intraocular pressure (IOP) of 17.1±6.6 mmHg. During follow-up the IOP decreased by 14% in these eyes but MD deteriorated by 1.1±3.5 dB/year, which was 5-fold higher than controls (0.2±1.6 dB/year). In a multivariate model, the best predictors for blindness by glaucoma were initial MD (p<0.001), initial IOP (p<0.001), older age at the beginning of follow-up (p<0.001), whereas final IOP was found to be protective (p<0.05). CONCLUSIONS: In this series of patients, blindness occurred in about 20%. Blindness by glaucoma had 2 characteristics: late diagnosis and/or late referral, and progression of the disease despite in most cases IOP was within the range of normality and target IOP was achieved; it could be predicted by high initial MD, high initial IOP, and old age.

Effectiveness and tuberculosis-related safety profile of interleukin-1 blocking agents in the management of Behçet's disease.

Behçet's disease (BD) is a multi-systemic disorder of unknown etiology characterized by relapsing oral-genital ulcers, uveitis, and involvement of the articular, gastrointestinal, neurologic, and vascular systems. Although the primum movens of this condition remains unknown, a tangled plot combining autoimmune and autoinflammatory pathways has been hypothesized to explain its start and recurrence. In-depth analysis of BD pathogenetic mechanisms, involving dysfunction of multiple proinflammatory molecules, has opened new modalities of treatment: different agents targeting interleukin-1 have been studied in recent years to manage the most difficult and multi-resistant cases of BD. Growing experience with anakinra, canakinumab and gevokizumab is discussed in this review, highlighting the relative efficacy of each drug upon the protean BD clinical manifestations. Safety and tolerability of interleukin-1 antagonists in different doses have been confirmed by numerous observational studies on both large and small cohorts of patients with BD. In particular, the potential for Mycobacterium tuberculosis reactivation and tuberculosis development appears to be significantly lower with interleukin-1 blockers compared to tumor necrosis factor-α inhibitors, thus increasing the beneficial profile of this approach.

Spinal administration of mGluR5 antagonist prevents the onset of bortezomib induced neuropathic pain in rat.

Peripheral neuropathy is a common adverse effect of bortezomib-based chemotherapy. In this study we have investigated the role played by subtype 5 of metabotropic receptors in bortezomib induced peripheral neuropathy. Rats were administered with bortezomib three times weekly at 0.20 mg/kg for a total of 4 weeks in presence or absence of mGluR5 antagonist MPEP. The animals were submitted to paw-pressure test and tail sensory nerve conduction measurement more times during the treatment and follow-up. Bortezomib treatment induced a progressively increasing hyperalgesia in rat which was accompanied by a significant reduction in sensory nerve conduction velocity (SNCV). MPEP prevented the emergence of bortezomib-induced pain and counteracted SNCV reduction when co-administered with bortezomib treatment. Spinal extracellular glutamate levels increased in rats treated with bortezomib. Bortezomib-induced onset of the hyperalgesia and SNCV decrease could be prevented by agents that promote the reuptake of glutamate maintaining spinal glutamate at basal level. Our data support the manipulation of the glutamatergic system through the mGluR5 receptor in bortezomib induced peripheral neuropathy. The use of antagonists at the mGluR5, initiated at the same time as bortezomib-chemotherapy, might reduce the number of patients who develop painful peripheral chemo-neuropathy.

Prophylactic role of acetyl-l-carnitine on knee lesions and associated pain in a rat model of osteoarthritis.

AIMS: in the present study, our aim was to validate in vivo the prophylactic role of acetyl-l-carnitine (ALC) using an established knee osteoarthritis (OA) animal model which mimics the pathological changes of OA in humans, targeting cartilage and causing chondrocyte death. MAIN METHODS: animal model was obtained by an intra-articular injection of monosodium iodoacetate (MIA) into rat femorotibial joint space. Pain was measured in animals submitted to MIA model by paw pressure and compression behavioral tests in the presence or absence of ALC. KEY FINDINGS: morphological analysis of knee-joint from MIA and ALC co-treated rats showed that the total pathological score attributed to histological findings was dramatically lower in rats treated with MIA in the presence of ALC. OA chondrocyte overexpression of pathogenic collagenase matrix-metallopeptidase-13 (MMP13) could be decreased in knee-cartilage from MIA/ALC rats; whereas type II collagen (COL2) expression level could be partially increased to control value. ALC twice daily treatment was able to attenuate pain in OA rat knee as revealed by mechanical behavioral tests. SIGNIFICANCE: in our experiments, pain that is usually associated with OA, was correlated with the severity of histopathological findings. Our findings show that there is a place for ALC as chondroprotective agents in cartilage degradation and strongly support the prophylactic and therapeutic potentials of ALC in knee-OA patients.

In vivo confocal microscopy of conjunctiva in preservative-free timolol 0.1% gel formulation therapy for glaucoma.

PURPOSE: To evaluate the effects at 1 year of preservative-free timolol gel and preserved timolol eye drops on conjunctiva and tear parameters. METHODS: Forty patients with primary open-angle glaucoma or ocular hypertension were randomized to the two treatment groups and compared with 20 healthy age-matched controls. Clinical tests (IOP, Schirmer I test, and lacrimal film break-up time BUT) and in vivo conjunctival confocal microscopy (IVCM) were performed in all patients at baseline and after 12 months. IVCM (HRT II Rostock Cornea Module; Heidelberg Engineering GmbH, Heidelberg, Germany) was performed after topical anaesthesia in the four cardinal locations and at the corresponding limbus to analyse conjunctiva cells. The main IVCM outcomes were goblet cell density and epithelial regularity. RESULTS: IVCM and clinical parameters were similar in the three groups at baseline. After 12 months, intra-epithelial goblet cell density was significantly lower in the preserved (48.25 ± 7.70) than in the preservative-free beta-blocker group (86.83 ± 22.17, p < 0.001) and controls (88.9 ± 18.33, p < 0.001). The epithelial layer was significantly more regular in the preserved beta-blocker medication group than in the preservative-free beta-blocker group (p < 0.001) and the control group (p < 0.001). A significant reduction in both Schirmer I and BUT was found in the group of preserved timolol (respectively, 11.3 ± 2.97 and 8.12 ± 0.99) compared with preservative-free timolol (16.8 ± 1.83 and 11.27 ± 1.27, p < 0.001) and controls (17.8 ± 1.87 and 12.10 ± 1.28, p < 0.001). CONCLUSIONS: Based on our IVCM data, preservative-free beta-blocker gel induces less changes at ocular surface than preserved beta-blockers, a fact that should be considered to obtain less adverse effects and maximal adherence to treatment in a chronic condition such as glaucoma.

Dual effect of morphine in long-term social memory in rat.

BACKGROUND AND PURPOSE: Bimodal dose-response relationships have been demonstrated in animals and humans following morphine administration. We examined if systemic administration of morphine, in extremely low (µg) and high (mg, analgesic) doses, changed the learning process. EXPERIMENTAL APPROACH: In the social learning test, an adult rat investigates a juvenile. The juvenile is submitted to a second encounter after a few days and investigation by the adult should be reduced. Morphine was administered before the first encounter between rats, and the critical test was performed 24, 72 or 168 h later, when animals were re-exposed to each other, in the absence of morphine. KEY RESULTS: Low doses of morphine, comparable with endogenous brain concentrations, enhanced long-term memory recognition; while high doses did the reverse, indicating the adult failed to recognize the juvenile. Recognition of a familiar rat appeared to be mediated within the brain accessory olfactory bulb (AOB) by an opioid system intrinsic to the olfactory system through µ-opioid receptors (MORs). At this supraspinal site, the PLC/PKC signalling pathway was activated by extremely low morphine doses. CONCLUSIONS AND IMPLICATIONS: Morphine treatment administration may either disrupt or facilitate social memory, depending on the dose, extending to memory formation the bimodal effects of morphine previously shown in pain. Social memory formation elicited by extremely low morphine doses, was mediated within the AOB by an opioid system, intrinsic to the olfactory system through MORs.

13q deletion syndrome and retinoblastoma in identical dichorionic diamniotic monozygotic twins.

PURPOSE: To report the case of identical dichorionic diamniotic female twins with unilateral retinoblastoma in 13q deletion syndrome. METHODS: Clinical and ophthalmoscopic evaluation, combination of multiple ligation-dependent probe amplification, array-comparative genomic hybridization analyses, and magnetic resonance imaging were performed. RESULTS: Peculiar facial features, marked hypotonia, gastroesophageal reflux, interatrial septal defect with left to right shunt and light dilatation of right chambers, 5th finger hypoplasia, 3rd-5th toes clinodactyly, 2nd toe overlapped to 3rd toe, and cutis marmorata were found. Ophthalmoscopic evaluation revealed unilateral retinoblastoma in both girls. Magnetic resonance imaging detected corpus callosum hypoplasia in both twins. A 34.4-Mb deletion involving bands 13q13.2-q21.33 and including the RB1 gene was identified in both twins. The deletion was not present in the DNA of their parents and older brother. CONCLUSIONS: Dysmorphic features in children must be always suspicious of 13q deletion syndrome and a short ophthalmoscopic follow-up is necessary to detect the presence of a retinoblastoma.

Contribution of G inhibitory protein alpha subunits in paradoxical hyperalgesia elicited by exceedingly low doses of morphine in mice.

AIMS: Although morphine, at higher doses, induces analgesia, it may also enhance sensitivity to pain at extremely low doses as shown in studies for testing an animal's sensitivity to pain. We used an antisense approach capable of selectively down-regulating in vivo G(i)(G inhibitory protein),G(o) and G(s) members of the G(α) sub-family protein subunits in order to establish if these proteins might be implicated in the effects induced by extremely low morphine doses on acute thermonociception. MAIN METHODS: Mice pretreated with a morphine hyperalgesic dose (1µg/kg) were submitted to hot plate test after pre-treatment with antisense oligodeoxynucleotides (aODNs) targeting G(iα), G(oα) and G(sα) regulatory proteins. The association of G-protein (guanine nucleotide-binding regulatory protein) coupled receptors with G protein was investigated using co-immunoprecipitation procedure. KEY FINDINGS: The downregulation of the G(iα1-3) and G(oα1) proteins reversed the licking latency responses induced by 1µg/kg morphine administration toward the basal value whereas downregulation of the G(oα2) and G(sα) proteins did not significantly modify the hyperalgesic response. SIGNIFICANCE: These results suggest that G inhibitory proteins play a role in the production of low dose evoked morphine hyperalgesia in mouse. Immunoprecipitation studies revealed that both µ opioid receptor (µOR) and α(2) adrenoreceptor (α(2) AR) are bound to G inhibitory proteins in hyperalgesic response to morphine extremely low dose. Both µOR and α(2) AR appear to be necessary for low morphine dose induced hyperalgesic response through G inhibitory proteins.