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Abstract Accurate segmentation of pupil light reflexes is essential for the reliable assessment of ptosis severity, a condition characterized by the drooping of the upper eyelid. This study introduces a novel encoder-decoder network specialized in reflex segmentation by focusing on addressing issues related to very small regions of interest from an architectural perspective. Specifically, the proposed network is designed to exploit low-level features effectively by integrating a multi-level skip connection and a 1 × 1 convolution-enhanced initial encoding stage. Assessed using a photograph image dataset from Chung-Ang University Hospital, which includes 87 healthy subjects, 64 with ptosis, and 257 with Graves’ orbitopathy (collected between January 2010 and February 2023), the proposed network outperforms five conventional encoder-decoders. Over 30 trials, the proposed network achieved a mean Dice coefficient of 0.767 and an Intersection over Union of 0.653, indicating a statistically significant improvement in the segmentation of reflex. Our findings show that an elaborate design based on the lowest-level skip connection and 1 × 1 convolution at initial stage enhances the segmentation of pupil light reflexes. The source code of the proposed network is available at https://github.com/tkdgur658/ReflexNet .

Introduction: Pituitary apoplexy is a rare endocrine emergency that is occasionally life-threatening, most often involving pituitary macroadenomas. Most pituitary macroadenomas are nonsecretory and are diagnosed in the late stages. They remain undiagnosed until they cause compression of the surrounding vital structures and lead to subsequent symptoms. The clinical feature depends on the size of the tumor and the direction of the spread. There are two approaches for surgery. The less invasive endoscopic transnasal transsphenoidal approach is favored more than the transcranial approach. Case Report: 46-year-old female patient presented to the outpatient department (OPD) with complaints of headache and drooping of the right eyelid for 1.5 months. On neurological examination, right severe ptosis was present and extraocular movements of the right eye are restricted for the muscles supplied by the third nerve. Pupils were reactive to light. On perimetry, the left eye showed temporal hemianopia. Right eye perimetry was not done due to ptosis. MRI Brain gave differential diagnosis as pituitary macroadenoma with hemorrhage or necrosis and pituitary apoplexy without macroadenoma. Endoscopic transnasal transsphenoidal excision of the tumor under general anesthesia was performed. Conclusion: MRI brain is the preferred imaging for cases with high suspicion of pituitary apoplexy. Endoscopic transnasal transsphenoidal excision of the tumor is an excellent choice for surgical resection of pituitary adenomas, with improved rates of complete tumor removal and reduced incidence of complication.

Metastasis to the skull base is a rare but serious complication of various malignancies. This case report discusses a 50-year-old woman with a history of advanced endometrialadenocarcinoma who presented with progressive headache, left-eye blindness, and ptosis. Imaging revealed a mass along the left optic nerve, raising suspicions of mucormycosis, but biopsy confirmed metastatic endometrial adenocarcinoma. Despite undergoing skull base radiotherapy, the patient’s vision did not improve. This case underscores the importance of considering metastatic endometrial adenocarcinoma in differential diagnoses for skull base lesions, particularly when other conditions are ruled out. Accurate diagnosis requires careful integration of clinical, radiological, and histopathological data.

An inflammatory myofibroblastic tumour (IMT) is a rare neoplasm of mesenchymal origin, defined by myofibroblastic spindle cells accompanied by inflammatory cells, lymphocytes and eosinophils. Its symptomatology depends on the involved site and tends to mimic a malignant tumour clinically and radiologically. The head and neck region accounts for 5% of all IMTs. Here, we report a case of a 35-year-old woman, with no medical history, who presented with a mouth-opening limitation of 8 mm evolving for three years and occurring six months after of a wisdom tooth extraction. She also experienced a recent occurrence of left eye ptosis and a converging strabismus. On examination, the patient had a body temperature at 37°C, with hypoesthaesia of the left chin and infraorbital area, without any other abnormality. Laboratory examinations did not reveal a biological inflammatory syndrome or rhabdomyolysis. The infectious investigations were all negative, as well as the immunological tests, in particular negative for anti-AChR and anti-MuSK antibodies. On the facial computed tomography (CT) scan, we noted an active reshuffle in the left mandible ascending branch with a thickening of the ipsilateral pterygoid muscles and the left temporal meningeal tissue. After corticosteroid therapy 0.7 mg/kg/j, we obtained an improvement in the patient’s mouth-opening, thus a biopsy of the lesion was performed under local anaesthesia, revealing IMT. The patient continued the corticosteroids therapy with a progressive tapering resulting in a marked clinical improvement of the mouth-opening limitation and her ptosis.

Key Clinical Message Ptosis associated with rhinosinusitis may indicate orbital or cavernous sinus involvement, typically accompanied by various other symptoms. However, isolated ptosis is a rare occurrence. This explains the diverse treatment approaches found in this literature review, ranging from conservative management to surgery. Imaging plays a crucial role in diagnosis and treatment planning. Abstract Isolated upper lid ptosis is a rare manifestation of acute rhinosinusitis, typically occurring without other neuro‐ophthalmological or orbital signs. This report presents a case of unilateral isolated ptosis in an adult male with acute rhinosinusitis. A 30‐year‐old male with asthma and bipolar disorder, and recent intranasal drug use, presented with nasal congestion, facial pressure, headache, and left eye droopiness. Neurological examination found left ptosis as the only abnormality. Lab results were normal, and COVID‐19 PCR was negative. Imaging showed pansinusitis without complications. The patient received IV antibiotics and steroids, followed by oral antibiotics and steroids. Ptosis resolved within 3 days and did not recur at three‐month follow‐up. Only seven cases of isolated ptosis with rhinosinusitis have been reported, all in males, most recovering with medical therapy alone. This is the first case treated with high‐dose steroids in addition to antibiotics. Isolated ptosis may be due to inflammation of the oculomotor nerve's distal branch or related muscular structures. Isolated ptosis in rhinosinusitis has a favorable prognosis. Imaging is crucial to exclude severe complications. The role of steroids needs further evaluation, and the timing for considering surgery remains to be defined.

Key Clinical Message Filler injections into the upper eyelid may cause levator aponeurosis fibrosis and ptosis. This risk must be considered. When ptosis appears, treatment might be difficult. Understanding the upper eyelid anatomy and procedures is essential to prevent eyelid damage. Abstract Ptosis is a prevalent condition in cosmetic surgery that occurs due to malfunction of the levator palpebrae superioris or insufficient Müller muscle action. It is characterized by the upper eyelid edge appearing lower than usual when seen at eye level. Ptosis may be categorized into congenital and acquired forms. The primary cause of congenital ptosis is attributed to abnormalities of the levator palpebrae superioris muscle or the motor nerve innervation that controls it. The condition arises from atypical development and malfunction of the oculomotor system. Acquired ptosis may be classified into many categories including traumatic, neurogenic, myogenic, senile, mechanical, and fake ptosis. Currently, there is little documentation of ptosis resulting from the degeneration of the aponeurosis of the muscle in the upper eyelid. We received a case of ptosis caused by fibrosis of the levator palpebrae superioris aponeurotic membrane. We used the technique of levator palpebrae superioris great advancement. The levator palpebrae superioris—Müller muscle was folded to create a stable composite construction via the levator palpebrae superioris high progress.

Acute Subdural Haemorrhage (SDH) frequently arises as a complication after head trauma, often resulting in sudden loss of consciousness and neurological impairments in an individual who was previously healthy [1]. Uncommonly, a ruptured aneurysm may present with SDH. Among these cases, a ruptured aneurysm at the junction of the Internal Carotid Artery (ICA) and the Posterior Communicating Artery (Pcom) stands out as the most common site associated with this uncommon spontaneous acute SDH [2]. This manuscript documents imaging and endovascular management of a rare case of a ruptured Pcom aneurysm presenting as acute SDH. The purpose of presenting this case was to underscore awareness of this condition, helping to prevent diagnostic and therapeutic errors

Objectives:The aim of this study was to investigate the incidence of postoperative ptosis after primary trabeculectomy and the possible factors contributing to ptosis.Materials and Methods:A total of 312 patients (339 eyes) who underwent trabeculectomy with mitomycin-C between 2015 and 2020 were retrospectively evaluated. Patients who had regular follow-up for at least 6 months and no history of ptosis or ptosis surgery were included. Age, sex, glaucoma type, preoperative and postoperative intraocular pressure, preoperative and postoperative antiglaucoma medications, number of antiglaucoma drops, duration of antiglaucoma medication use, history of eye itching due to antiglaucoma medication-associated allergy, duration of follow-up, postoperative needling, needling time, and ocular massage were recorded. Ptosis was defined as ≥2 mm reduction in margin-reflex distance 1 from preoperative levels. Ptosis that had not improved for at least 6 months was considered persistent ptosis. Multivariate logistic regression was used to determine potential predictors of ptosis development.Results:Ptosis after trabeculectomy was observed in 35 of 339 eyes (10.3%). Thirty eyes of 30 patients (8.8%) had transient ptosis and 5 eyes of 4 patients (1.5%) had persistent ptosis. Preoperative duration of antiglaucoma medication use, drug(s) used (prostaglandin analogs, beta-blockers, alpha-2 agonists, carbonic anhydrase inhibitors, or combinations of these), needling time, and ocular massage after trabeculectomy did not differ significantly between groups (p>0.05). Rates of needling and eye itching due to antiglaucoma medication-associated allergy were significantly higher in patients with ptosis (p

Systemic lupus erythematosus （SLE） is a chronic connective tissue disease affecting multiple organ systems of the body， whereas the etiology of SLE has not been fully clarified. SLE complicated with intracranial aneurysm is rare， which is mostly seen in SLE patients who have been diagnosed for many years and the disease is uncontrolled. Most SLE patients complicated with intracranial aneurysm have no symptoms， while some patients present with headache， nausea or central nervous system symptoms caused by the aneurysm. Here， we reported a case of newly-diagnosed SLE complicated with the right eyelid ptosis caused by intracranial aneurysm compression of the right oculomotor nerve during treatment. After standard drug therapy combined with cerebral vascular interventional surgery， the right eyelid ptosis was rapidly mitigated. The diagnosis and treatment of this patient prompt that the possibility of intracranial aneurysm should be considered when SLE patients develop dizziness， headache， vomiting or nerve compression symptoms. Standard drug therapy combined with surgical intervention should be performed when the diagnosis is confirmed， aiming to prevent the incidence of severe complications， such as aneurysm rupture or carotid-cavernous fistula.

Abstract Here we report the evaluation of the frequency of subjective and objective otolaryngologic findings and therapeutic results in 32 patients with mitochondrial encephalomyopathy (MEM) from September 2001 to June 2021. Our analysis included studying the patients’ family histories, the clinical manifestations of MEM, and the therapeutic effects of treatments. The patients’ ages ranged from 2 to 77 years, with a median age of 12.3 years. We found that MEM ENT symptoms were characterized by hearing loss, dysphagia, and facial weakness. Most cases of sensorineural hearing loss were bilateral symmetrical progressive or sudden deafness since adolescence, which were often underestimated. Associated neuromuscular symptoms required mtDNA testing. Dysphagia and facial weakness occurred preferentially in middle-aged patients, and muscle biopsies were advised. Distortion product otoacoustic emissions and auditory brainstem responsetesting were more sensitive and reliable than pure tone averages for objective monitoring of pathogenesis. Administration of the mitochondrial synthase complex benefited patients with acute episodes. If patients did not fully recover and exhibitedresidual language deficits, hearing aids or cochlear implants were recommended. Counsel was given regarding synthetical treatments for facial weakness, endoscopic circopharyngealmyotomy for dysphagia, and surgical correction of ptosis. This study demonstrates that increased awareness of these symptoms is important to address appropriate interventions and avoid complications such as ablepsia, aphasia, social isolation, malnutrition, aspiration pneumonia, and heart failure in the setting of MEM.

Key Clinical Message Prompt diagnosis and treatment of GCA are crucial to preserve vision. Because of this, new‐onset ptosis or diplopia in elderly patients should warrant consideration of GCA, even in the absence of “classic” features, systemic symptoms or elevated inflammatory markers. Abstract Giant cell arteritis (GCA) is a vision‐threatening, ophthalmic emergency that classically presents with new‐onset headaches, scalp tenderness, systemic symptoms, visual disturbances, and elevated inflammatory markers. We describe an atypical presentation of GCA in an 87‐year‐old patient with fatigable ptosis and diplopia, with subsequent anterior ischemic optic neuropathy and choroidal infarction.

A 32-year-old man presented with complete third nerve palsy. Brain magnetic resonance imaging revealed a possible sporadic oculomotor nerve schwannoma in the left cavernous sinus. Interestingly, the patient’s ptosis was fluctuating and eased immediately after application of ice over his eyelid. The ice pack test (IPT) is a simple and fast method that can help diagnose myasthenia gravis (MG) in patients with ptosis. Additional diagnostic investigations (antibody assays and repetitive stimulation) excluded associated MG in the patient. Tumor treatment with Gamma Knife radiosurgery was planned. This case highlights the finding that IPT can also be positive in neurogenic (non-myasthenic) ptosis, but its usefulness in other disorders associated with muscle weakness and fatigability remains questionable.

A 20-year-old woman presented with left eye ptosis without any headache and pupillary dysfunctions. After the radiological examination, the oculomotor nerve compression was detected in the interpeduncular space by the posterior communicating artery (PCoA) with normal size and shape. The patient underwent frontotemporal craniotomy, and during the surgery, the nerve was detached from the PCoA. Immediately after surgery, all symptoms disappeared. Although oculomotor nerve palsy (ONP) owing to internal carotid-PCoA aneurysm is common, vascular compression due to a non- aneurysmal PCoA is very rare. To the extent of our knowledge, this is the first case in which a slightly displaced, otherwise normal, PCoA causes ONP without any pupillary involvement. After ruling out an aneurysmal artery, this should be considered as one of the possible causes of the ONP.

Despite increasing information on Pseudoangiomatous Stromal Hyperplasia of Breast (PASH), the challenges of management of giant PASH remain for the surgeon. A pragmatic and individualized approach is the solution in the absence of reliable algorithms for management. This instance of a giant PASH tumor producing gigantomastia with severe ptosis is a case to point. When PASH presents as a giant mass, leading to gigantomastia with inevitable severe ptosis, the surgical options range from the excision of mass with reduction mammoplasty or a simple mastectomy with or without reconstruction. The key to surgical decision-making is individualization of surgery.

Abstract Purpose The ectodermal dysplasias (EDs) constitute a group of disorders characterized by abnormalities in two or more ectodermal derivatives, including skin, hair, teeth, and sweat glands. The purpose of the current study was to evaluate ocular manifestations in pediatric patients with ED. Methods Retrospective case series including consecutive ED subjects who were treated in the ophthalmology department at the Children’s Hospital of Philadelphia over a 12-year period (2009–2020). Main Outcome Measures were ocular and ocular adnexal abnormalities. Results Thirty subjects were included: 20 males (67%), mean age of 4.5 years (range 0.3–18). Patients with different subtypes were included, with the hypohidrotic ED and ectrodactyly-ectodermal dysplasia-clefting variants being most prevalent. Most common findings were: lacrimal drainage obstruction in 12 (40%) including punctal agenesis in 10 (33%), refractive errors in 13 (43%) and amblyopia in 6 (20%). A new finding of eyelid ptosis or eyelash ptosis was demonstrated in 11 subjects (37%), mostly associated with TP63 or EDA1 genes variants. Conclusion Ectodermal dysplasias are associated with various ocular pathologies and amblyopia in the pediatric population. We report a possible genetic association between lash ptosis and EDA1 gene, and eyelid ptosis and TP63 or EDA1 genes variants.

We present the case of a patient with paramedian mesencephalic and ipsilateral thalamic infarction with an unusual clinical presentation, where the diagnosis and accurate anatomical localization were imperative for a unique clinicoradiological correlation. Our patient was a 42-years old, right-handed Indian gentleman with hypertension who presented following acute myocardial infarction. He developed acute diplopia, left ptosis and right eyelid retraction. There was an associated hemiataxia and diminished sensation in right half of body. Plus-minus lid syndrome and hemiataxia - hypesthesia are two different clinical syndromes. A co-association of these two syndromes in the same patient is rare which was evident in our case.

Acute ptosis due to preseptal cellulitis requires urgent medical attention, as the infection can extend posteriorly into the orbit, leading to significant visual and cerebral complications. We report a case of a 58-year-old woman with uncontrolled diabetes mellitus presenting with acute ptosis due to preseptal cellulitis. After initial resolution of fever with intravenous amoxicillin-clavulanate, she experienced a seizure due to cerebral abscess a week later and was treated with intravenous ceftriaxone. Preseptal cellulitis is usually treated on an outpatient basis with oral antibiotics, as it rarely extends posteriorly to cause cerebral complications. We wish to highlight the importance of admitting patients with preseptal cellulitis in patients with uncontrolled diabetes for intravenous antibiotics due to the potential for visual and cerebral complications.

Abstract Hypopituitarism secondary to a pituitary metastasis is rare and difficult to diagnose since its symptoms are nonspecific. The presence of visual deficits and nerve palsies should suggest the presence of a pituitary metastasis in a cancer patient.

A 57-year-old female presented with headache, miosis, and ptosis diagnosed as Horner syndrome (HS). After delaying the recommended diagnostic imaging, she experienced transient, unilateral visual impairment in bright light. The patient was subsequently determined to have a spontaneous internal carotid artery dissection (ICAD) and secondary retinal ischemia with minimal cardiovascular risk factors and no history of preceding trauma. She wore dark glasses, received gabapentin for pain control, and was anticoagulated for a total of 4 months at which time the ICAD resolved despite a residual blepharoptosis and anisocoria.

Abstract Background The trigeminal autonomic cephalalgias are a group of primary headache syndromes marked by severe head pain and associated cranial autonomic symptoms which can include a full or partial Horner’s syndrome. Rarely, the eye-related symptoms will become fixed even between headache attacks. There is minimal documentation that the Horner’s syndrome can be reversed if successful treatment of the underlying headache disorder is initiated. Case reports Two cases are presented of trigeminal autonomic cephalalgia subtypes with chronic persistent Horner’s syndromes that alleviated with treatment of the underlying primary headache disorder. Patient 1, an 82-year-old Caucasian woman, presented with hemicrania continua with a partial Horner’s syndrome that was present for 2 years. She was unable to take indomethacin as she was on anticoagulation. After a C2–3 diagnostic facet injection, not only did she become pain free but her ptosis completely resolved. She then underwent a radiofrequency facet neurotomy with complete alleviation of head pain and complete resolution of her ptosis. Patient 2, a 21-year-old Caucasian woman, presented with long-lasting autonomic symptoms with hemicrania syndrome and a fixed miosis and ptosis of 6 months’ duration. After achieving 2 months of pain freedom on indomethacin her Horner’s syndrome completely resolved. Conclusion A chronic fixed partial or full Horner’s syndrome can occur in trigeminal autonomic cephalalgia subtypes, but it can also be reversed in patients with treatment even after months to years of duration. This would suggest that the sympathetic dysfunction leading to the eye-related symptoms is from irritation of the sympathetic chain rather than permanent injury as the result of vasodilatory trauma after trigeminal autonomic reflex activation.

Syphilis is a spirochete disease that occurs due to Treponema pallidum infection. It can be sexually transmitted and can be transmitted from mother to baby vertically. Neurological involvement is more common in the late period. The use of common antibiotics may alter the natural course of the disease. Because of this, syphilis may present with different neurological findings. A 49-year-old male patient was admitted to our clinic with complaints of fluctuating double vision and droopy left eyelid for two months. In the neurological examination, pupils were mid-dilated, direct and indirect pupillary light reflexes were bilaterally absent, movements of the left eye in all directions and rightward movement of the right eye were restricted. Also, bilateral ptosis was detected. Brain magnetic resonance imaging and electrophysiological studies including repetitive stimulation were normal. Syphilis was diagnosed with blood and cerebrospinal fluid (CSF) tests. He was treated with long-term high-dose intravenous penicillin. Ocular findings are an important indicator of neurosyphilis. Ocular involvement due to primary disease process is rare. If meningitis-related CSF absorption defect develops, eye movement disorders and pupil abnormalities may occur. The diagnosis of neurosyphilis may be delayed due to different clinical manifestations. Neurosyphilis should be considered in case of ocular findings.

Botulinum neurotoxin injection for treating glabellar frown lines is a commonly used method; however, side effects, such as ptosis and samurai eyebrow, have been reported due to a lack of comprehensive anatomical knowledge. The anatomical factors important for the injection of the botulinum neurotoxin into the corrugator supercilii muscle has been reviewed in this study. Current understanding on the localization of the botulinum neurotoxin injection point from newer anatomy examination was evaluated. We observed that for the glabellar-frown-line-related muscles, the injection point could be more accurately demarcated. We propose the injection method and the best possible injection sites for the corrugator supercilii muscle. We propose the optimal injection sites using external anatomical landmarks for the frequently injected muscles of the face to accelerate effective glabellar frown line removal. Moreover, these instructions would support a more accurate procedure without adverse events.

Snake bite is a major life-threatening emergency seen more commonly in rural tropical countries. In general, about 70% of the bites are nonpoisonous, 15% are dry bites, and only 15% cause envenomation. Venom is the saliva of snake ejected during biting, from the poison apparatus (the modified parotid glands). It can be neurotoxic, vasculotoxic, or myotoxic in its action. The polyvalent antisnake venom is effective against most common poisonous snakes. Prompt diagnosis and timely administration of the polyvalent antisnake venom can reduce mortality and morbidity to a great extent. We present a case which was brought to the emergency department of without any previous forthcoming history of snakebite, with symptom such as abdominal pain, chest pain, vomiting, and respiratory distress followed by loss of consciousness. The patient was timely resuscitated and with prompt use of polyvalent ASV and neostigmine the patient recovered without any neurological symptoms within a week.

Aim: is to compare between the outcome and complications in the use of local and general anesthesia in the management of sever blepharoptosis by use of straight needle threading technique and silk suture as a frontalis suspension. Settings and Design: it’s a prospective comparative study using two group one under local anesthesia and the other under general anesthesia with standardization of the cases as all has sever ptosis and poor levator functions, technique as the straight needle threading technique was used, material of thread was silk in 92% of cases, and sex distribution was of no statistical significance. Methods and materials: The parameters used for comparison were the following:-Satisfaction, Correction, Symmetry, Lid crease height (visible pretarsal height), Infection, stich abscess, stich granuloma, Eye opening during sleeping, Lagophthalmus, Entropion, Exposure keratitis. A 120 eye was operated on 95 patients; 25 patients (50 eyes) bilateral, 70 patients (70 eyes) unilateral, 36 eyes (30%) were operated on under local anesthesia, and 84 eyes (70%) were done under GA. The minimal age was 2years, maximum age 75 years, median 12 years, mean 19.8 years. The patients above the age of 16 years old were asked to choose between local or GA while below that age the correction was done under GA only. Results: There was no statistical significant difference in the all the nine parameters except the eye opening during sleeping were higher in the general anesthesia group. Conclusion: The use of local anesthesia is easier, of less risk, and lower cost with same aesthetic results of general anesthesia.

Sphenoid sinus mucocele (SSM) is rare and constitutes 1-2% of all paranasal sinus mucoceles. In general, patients present with symptoms such as headache, swelling of the face, nasal obstruction, proptosis, disturbance of globe movements, diplopia and visual loss. In this article, we present a case of ophthalmoplegia which is diagnosed with rare SSM. A 72-year-old man was admitted with an upper respiratory tract infection and concomitant complaints of low left eye lid, diplopia and retroorbital headache. On examination, there were left ptosis and paralysis in all globe movements except for the outward gaze. The patients diplopia increased in downward gaze. Fundoscopy was normal. CT revealed a hypodense mass in the left sphenoid sinus that was compatible with a mucocele of about 3x2 cm. The patient was diagnosed with SSM and we performed emergency surgery. Sphenoid sinus mucoceles are very rare and benign lesions, but they can permanently damage the surrounding vital structures. Patients with headache and cranial nerve pathologies should be suspected of SSM. Surgical treatment of SSM by transnasal endoscopic approach can be preferred because of its ease of application and low morbidity and recurrence rates. Early surgical intervention can prevent the damages that will develop in patients. [Med-Science 2018; 7(1.000): 229-231]

Physiologic pituitary enlargement is common during normal pregnancy. However, symptoms such as diplopia, blurred vision and headache resulting from physiologic pituitary enlargement are very rare during pregnancy. A 43-year-old woman complained of sudden headache and left eye ptosis at 36th weeks of gestation. An magnetic resonance imaging (MRI) demonstrated the pituitary enlargement and a macroadenoma without a compressing of the optic chiasm, but with an extension to the left cavernous sinus. 48 hours after the prescription of the bromocriptine, we had a spectacular evolution with disappearance of the headache and a total regression of the ptosis. We report a case of visual loss due to the physiologic pituitary enlargement or to the macroadenoma during pregnancy, which regressed after the prescription of bromocroptine.