Estimation of angle parameters by ASOCT and biometric parameters by optical biometer in eyes with occludable angles and open angles.

PURPOSE: To compare anterior chamber angle (ACA) parameters measured by Anterior Segment Optical Coherence Tomography (ASOCT) and biometric parameters measured by Swept-Source (SS) OCT-based biometry among patients with suspected occludable angles and open angles. METHODS: An analytical, cross-sectional study was performed on subjects attending our ophthalmology outpatient department with suspected occludable angles (van Herick grades 0, 1, and 2) in group 1, and with open angles (van Herick grades 3 and 4) in group 2. Each subject underwent a complete ophthalmic examination to exclude any intraocular pathology like cataract. We recruited 128 eyes of 64 subjects, 34 in group 1 and 30 in group 2. Each eye was henceforth subjected to ASOCT (Spectralis, Heidelberg Engineering, Heidelberg) and SS-OCT-based optical biometry (IOL Master 700, Carl Zeiss Meditec AG). Anatomical parameters were recorded and compared between the two groups. RESULTS: The main outcome measures of the study included nine ASOCT parameters (central corneal thickness [CCT], lens vault, AOD750, ACA, TISA750 [nasal and temporal], and ACW) and five optical biometric parameters (CCT, ACD, WTW, LT, and axial length). We found a significant difference (p < 0.05) among all the anatomical parameters between the two groups, except CCT which was not significantly different (p = 0.297). CONCLUSIONS: ASOCT and SSOCT biometry overcome the challenges of gonioscopy and allow screening for angle closure disease in otherwise normal subjects. ASOCT may serve as an alternative to gonioscopy as it clearly separates occludable angles from open angles in a non-invasive and objective manner.

Development of ezetimibe eutectic with improved biopharmaceutical and mechanical properties to design an optimized oral solid dosage formulation.

Eutectics are multicomponent systems which are an alternative to the conventional techniques for modulating the biopharmaceutical properties of a pharmaceutical. Ezetimibe (ETZ) is a hypocholesterolemic agent with limited dissolution, poor water solubility, and subsequently demonstrates low oral bioavailability. Additionally, ETZ exhibits poor mechanical properties, leading to difficulties in developing dosage forms through direct compression. The present work highlights the applicability of eutectics in the simultaneous improvement of physicochemical along with mechanical properties of ETZ. A pharmaceutical eutectic of ETZ with succinimide (SUC) was prepared by mechanochemical grinding and thoroughly characterized using thermoanalytical, X-ray diffraction, and spectroscopic methods. Intrinsic dissolution rate and pharmacokinetic analysis were also performed for ezetimibe-succinimide (ETZ-SUC) eutectic in contrast to pure ETZ. The eutectic demonstrated ∼2-fold increase in the solubility and dissolution rate. In pharmacokinetic studies, the area under the curve (AUC) for ETZ-SUC eutectic (28.03 ± 2.22 ng*h/mL) was found to be higher than ETZ (8.98 ± 0.36 ng*h/mL), indicating improved oral bioavailability for eutectics. Also, it was observed that enhanced material functionality aids in designing directly compressed tablets, where the eutectic formulation showed an improved dissolution profile over the ETZ formulation. The study demonstrates that eutectic conglomerates could be utilized to develop ideal oral solid dosage formulations.

Intraoperative floppy iris syndrome: an updated review of literature.

Intraoperative Floppy iris syndrome(IFIS) remains a challenge for surgeons during phacoemulsification. Initially, it was related to the use of tamsulosin, an alpha adrenergic receptor blocker used in benign prostatic hyperplasia. Subsequently, other alpha adrenergic receptor such as alfuzosin, terazosin and doxazosin alongwith different other class of medications and systemic risk factors were identified. Other class of medications includes 5-alpha reductase inhibitor, angiotensin receptor antagonist, benzodiazepines, antipsychotics and antidepressants. Other risk factors include increasing age, male gender, diabetes, hypertension and decreased preoperative pupil diameter. It is very important for surgeons to identify these risk factors preoperatively and take appropriate preoperative and intraoperative measures to tackle the dreaded complications of IFIS. Sometimes, it is important for an ophthalmologist to work in cooperation with physician and urologist to minimize the complications. In conclusion, awareness of the risk factors associated with IFIS, their detailed preoperative assessment and intraoperative measures and surgical intervention is crucial in addressing IFIS. Lack of awareness can turn a routine, uneventful surgery into one with significant visual morbidity.

Donor demographics and factors affecting corneal utilisation in Eye Bank of North India.

INTRODUCTION: Nearly 6.8 million people in India have vision less than 6/60 in at least one eye due to corneal diseases; of these, about a million had bilateral involvement. PURPOSE: To identify the challenges faced; the trends in collection, storage and utilisation of corneal tissues in an eye bank in north India. MATERIALS AND METHODS: The past records of Eye Bank linked to a tertiary hospital in northern India were analysed from November'1999 to October'2015 with respect to number of eye donations per year, donor demographics and utilisation of corneal tissues. RESULTS: The number of donations during the first 6 years were 100, 279 in the next 5 years and 473 in the last 5 years. The mean donor age was 63.2 ± 19.5 years. The percentage of donors less than 30, 31-60 and more than 60 years was 10%, 28% and 62%. Forty-two percent donations were from the hospital. The average time between the death and enucleation was 4.74 ± 5.31 hours. The percentage of corneas used in the donor age groups less than 30, 31-60 and above 60 years was 61.9%, 61.6% and 53.8%, respectively. The usability rate of the corneas from home and hospital was 63.7% and 55.3%, respectively. CONCLUSIONS: The eye bank had a lukewarm response in the beginning, but gained momentum with time. The myths and beliefs prevalent in our society deter people from donating eyes freely. Each eye bank needs to individualise its problems and find solutions for adequate procurement and utilisation of tissue.

Changes in ocular surface status after phacoemulsification in patients with senile cataract.

AIM: To evaluate the signs and symptoms of dry eye after phacoemulsification; effects on the status of ocular surface using impression cytology; and associated risk factors. METHODS: Prospective study included 50 eyes (50 patients) with no dry eye signs or symptoms, who underwent clear corneal phacoemulsification for senile cataract. Dry eye indices used included Ocular Surface Disease Index scoring, Schirmer I test, tear break up time, tear meniscus height, corneal fluorescein staining, lissamine green staining and goblet cell density (GCD) with the help of impression cytology. Primary outcome measures included post-operative changes in the dry eye indices. Secondary outcome measures included correlation of the dry eye signs and symptoms with various risk factors. RESULTS: Aggravation of both the signs and symptoms of dry eye were noted in immediate post-operative period. The sharp deterioration was followed by a recovering trend towards the end of sixth week. A decrease in GCD was also noted. Risk factors for deterioration include age, duration of exposure to microscope light and effective phacoemulsification time. Diabetic status, socio-economic status and site of incision did not have any effect on dry eye status. CONCLUSION: There is a transient deterioration of "dry eye" status post-phacoemulsification. The patients should be carefully counselled about the evanescent nature of the disease. Incision can be given at the site of high corneal curvature to neutralize astigmatism without any fear of inducing dry eye. Minimum light exposure and ultrasound energy should be used during the surgery.

Indications and graft survival analysis in optical penetrating keratoplasty in a tertiary care center in North India: a 5-year study.

PURPOSE: To study the indications and variables correlating with graft survival in optical penetrating keratoplasty in a tertiary care hospital in north India. PARTICIPANTS: All patients who underwent optical keratoplasty, except those undergoing lamellar grafts, tectonic grafts transplants and penetrating keratoplasty done for therapeutic purposes were included in the study. Patients with follow-up less than 2 years were excluded from the study. MATERIALS AND METHODS: Data were obtained by reviewing the records of 101 patients who underwent optical penetrating keratoplasty from 2008 to 2013 for various indications. RESULTS: Out of 101 patients who underwent optical penetrating keratoplasty, 71 were males and 30 were females. The mean age of the recipient was 48.53 years with range 1-82 years. The main indications were previous failed graft (29.7%), healed keratitis except HSV (15.8%), pseudophakic or aphakic bullous keratopathy (14.8%), corneal dystrophies/degenerations (12.9%), adherent leucoma (9.9%), post-HSV scars (8.9%), and others like anterior staphyloma, congenital corneal opacities, buphthalmos and keratoconus (7.9%). The graft survival rate was 67.33% at 1-year follow-up and 59.4% at 2-year follow-up. The mean survival time of the grafts was 22.42 months. The mean time for graft failure was 7.12 (±0.9) months. CONCLUSION: One- and 2-year survival of grafts at our center is lower as compared to western studies, probably due to higher percentage of poor prognosis indications for surgery and a relative scarcity of excellent-quality donor corneas.

Adult onset retinoblastoma: A diagnostic dilemma.

Retinoblastoma is the most common intraocular tumor of childhood. About 95% of retinoblastoma cases are diagnosed before the age of 5 years. Not more than 30 cases of Adult-onset retinoblastoma have been reported in literature. A 32 year old male presented with a painful blind eye. There was sudden loss of vision accompanied by severe pain and redness in right eye about 1 year ago, for which some surgery was done with neither a gain in vision nor any relief from pain. Then he was put on maximum tolerable medical therapy, later cyclocryotherapy was done. Now he presented to us with complains of extreme pain and bleeding from right eye since 2 days. There is no history of any ocular trauma. Right eye had no perception of light & showed anterior staphyloma with perforation. Right eye evisceration was done & material sent for histopathological examination, which revealed an adult-onset retinoblastoma. CECT scan revealed thickening of optic nerve throughout its entire length with contrast enhancement. He was further taken up for enucleation of residual sclera with maximum optic nerve stump removal to reconfirm the diagnosis. Histopathological examination revealed tumor deposits present in orbital soft tissue, resection margins and optic nerve cut end.Retinoblastoma presenting in adult age creates a diagnostic dilemma because of its low frequency and atypical features. We want to highlight the importance of high clinical suspicion and imaging modalities before taking any patient for evisceration with unexplained vision loss. One should send the eviscerated material for histopathological examination.

Lid-wiper keratopathy and mucous membrane grafting.

BACKGROUND: A healthy lid-wiper is an important component of a healthy ocular surface. Any abnormality or irregularity of the lid wiper can potentially damage a relatively healthy ocular surface. Stevens-Johnson syndrome, toxic epidermal necrolysis, and ocular cicatricial pemphigoid are some of the examples that can result in lid-margin keratinization during the course of the disease. These permanent changes at the lid margin mechanically abrade the corneal surface and facilitate corneal neovascularization. The corneal clarity is lost over time, and the patients have corneal blindness. PURPOSE: This video discusses the role of a healthy lid-wiper, conditions causing lid-margin keratinization and subsequent lid-wiper keratopathy, and surgical technique in mucous membrane grafting. SYNOPSIS: The video demonstrates the technique of restoration of a healthy lid margin by doing a mucous membrane graft for lid-margin keratinization and its role in the prevention of corneal blindness. HIGHLIGHTS: Lid-margin keratinization is essentially a chronic sequela and is often ignored till irreversible corneal changes develop. Early intervention in the form of mucous membrane grafting can prevent corneal vascularization and loss of corneal clarity. VIDEO LINK: https://youtu.be/NGMlqUp_qLU.

Survival benefit of exenteration in COVID-19-associated rhino-orbital mucormycosis.

PURPOSE: There has been a sudden increase in the number of rhino-orbital mucormycosis cases, primarily affecting patients recovering from COVID-19 infection. The local health authorities have declared the current situation an epidemic. In this study, we assess the role of exenteration in preventing disease progression and improving survival in patients with rhino-orbital mucormycosis. METHODS: The patients undergoing exenteration were grouped into the exenteration arm and those denying exenteration were grouped into the nonexenteration arm. The patients were followed at 1 month and 3 months. The 6-month survival data were collected telephonically. Continuous data were presented as Mean ± SD/Median (IQR) depending on the normality distribution of data, whereas the frequency with percentages was used to present the categorical variables. Kaplan-Meier survival curves were created to estimate the difference in survival of patients with exenteration in rhino-orbital mucormycosis versus those without exenteration. RESULTS: A total of 14 patients were recruited for our study based on the inclusion and exclusion criteria. All the patients were qualified for exenteration; however, only eight patients underwent exenteration and six patients did not consent to exenteration. At the end of 3 months in the exenteration group, four (50%) patients died. Two patients died within a week of exenteration, whereas two patients died after 2 weeks of exenteration. The deaths in the first week were attributed to septic shock and the deaths happening beyond 2 weeks were attributed to severe meningitis. The Kaplan-Meier survival analysis showed the cumulative probability of being alive at 1 month in the exenteration arm to be 85%, and it decreased to 67% by 53 days and subsequently remained stable until the end of 3 months. CONCLUSION: The Kaplan-Meier survival analysis did not show a survival benefit of exenteration at 3 months and 6 months in COVID-associated rhino-orbital mucormycosis.

Role of tenon advancement in treating limbal ischemia in acute chemical injury.

Background: In acute chemical injury, damage can range from ocular surface epithelial defects to limbal and scleral ischemia. This may subsequently progress to corneal or scleral melting and perforation and finally result in phthisis bulbi. Thus, acute chemical injury is a potentially blinding condition and warrants attention. The accurate technique to assess the damage incurred should be practiced to avoid undertreatment and subsequent complications. Surgical intervention wherever needed should be appropriately timed and should be performed. The primary aim of medical or surgical intervention in acute chemical injury is to attain a stable and epithelized ocular surface. Even a conjunctival phenotype over the cornea is a desirable outcome. Purpose: This video discusses the nuances involved in the assessment and planning of Tenon advancement with amniotic membrane grafting for treating limbal ischemia in acute chemical injury. Synopsis: The video demonstrates the technique of restoration of limbal vascularization by performing Tenon advancement with amniotic membrane grafting and its outcome. Highlights: Ocular surface painting with fluorescein dye is essential to assess the areas of surface involvement. Merely instilling the fluorescein dye in the cul-de-sac will underestimate the extent of the damage. Tenon advancement should ideally be planned between 7 and 10 days following an injury when actual limbal blanching is obvious. A stable and epithelized ocular surface is the desirable outcome irrespective of the epithelial phenotype. Video Link: https://youtu.be/06XhwLKnsIA.

A cross-sectional study analyzing the correlation between the mean retinal nerve fiber layer and ganglion cell layer thickness with axial length and refractive errors among children aged 5-15 years.

Purpose: To analyze the correlation between the mean retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness with axial length and refractive errors among children aged 5-15 years. Methods: This cross-sectional, observational study was done on 130 eyes of 65 consecutive subjects with refractive errors. The patients were evaluated for RNFL thickness and macular GCL thickness using spectral domain- optical coherence tomography. Results: One hundred and thirty eyes of 65 subjects aged between 5 and 15 years were divided into three groups based on their spherical equivalent in diopters (D). The children with a spherical equivalent of ≤-0.50 D were considered myopic, ≥-0.5 to ≤+0.5 D were considered emmetropic, and ≥+0.50 D were considered hypermetropic. RNFL thickness and GCL thickness were correlated with age, gender, spherical equivalent, and axial length. The mean global RNFL thickness was 104.58 µm ± 7.567. Conclusion: There exists a negative correlation between RNFL thickness and macular GCL thickness with increasing severity of myopia and increase in axial length, and the possible reason could be stretching of the sclera, which further leads to stretching of the retina, resulting in thinner RNFL and macular GCL thickness.

Double capsular tension rings in cataracts with large subluxations.

Management of subluxated cataracts is challenging, especially in cases with more than 5 clock hours of subluxation. Capsular bag stabilising devices are of utmost importance in these cases. We report two cases of post-traumatic lens subluxation of more than 6 clock hours, in which the bag was stabilised intraoperatively using two capsular tension rings (CTRs) placed diametrically opposite to each other, in place of the conventional Cionni ring. Slow phacoemulsification was done followed by intraocular lens (IOL) implantation. Postoperatively, the IOLs were found to be well centred. Also, the use of two CTRs maintains the shape of the capsular bag and prevents lens epithelial cell migration and capsular cocontraction.

Demographic and microbiological profile of corneal ulcer patients presenting at a tertiary healthcare center of Eastern India during the COVID era: A hospital-based cross-sectional study.

Purpose: To determine the demographic and microbiological profile involved in the causation of corneal ulcers in Eastern India during the COVID era. Method: Patients presenting with corneal ulcers fulfilling the inclusion and exclusion criteria were taken as the case. The study duration was from January 2021 to December 2021. Socio-demographic details and information about risk factors were noted. A detailed corneal examination followed by corneal scraping was performed for microbiological evaluation. Results: In 1 year, 99 infective corneal ulcer patients were evaluated. Farmers (24.2%) were found to be maximally affected by corneal ulcers. The peak in cases was recorded from October to December (38.4%). Ocular trauma was the commonest risk factor (42.4%). The majority (80.8%) of patients were already on some topical antimicrobials. 22.2% of samples showed fungal filaments on KOH mount; 54.5% of these cases turned out to be culture-positive. 17.56% of KOH-negative samples turned out to be culture-positive (fungal). Overall, the culture positivity rate was 28.28% out of which fungal isolates were 89.28% and bacterial isolates were 10.72%. Fusarium species were identified as the most common organism contributing 42.85%, followed by Aspergillus fumigatus (14.28%). 10.72% of cases were culture positive for Pseudomonas aeuroginosa. Conclusion: Trauma with the organic matter was the predominant cause of fungal keratitis. In this study, fungal keratitis was found to be more common. Fusarium was the most common isolate.

A cross-sectional study to describe the spectrum of ocular manifestations and risk factors of mucormycosis presenting to a tertiary hospital of East India.

Purpose: To report the clinico-demographic profile of rhino-orbito-cerebral mucormycosis (ROCM) in patients during the "second wave" of the COVID-19 pandemic in eastern India, and their ophthalmic manifestations at presentation to our tertiary institute. Methods: Cross-sectional study amongst patients presenting to our center based on their hospital records. Demographic information, history related to COVID-19, records of detailed ocular examination, and microbiological, radiological, and histopathological investigation were entered into an online worksheet and analyzed using SPSS 26.0. Results: A total of 219 patients with ROCM were treated from May to September 2021, and 110 of these had ocular manifestations at presentation (50.2%). The age of patients ranged from 22 to 83 years and the mean ± standard deviation (SD) age was 49.9 ± 12.9 years. Ninety (81.8%) patients had been diagnosed with diabetes mellitus, 31 (34%) had hypertension, and 10 had other comorbidities. The duration between the onset of COVID-19 and mucormycosis symptoms was 0 to 60 days with a mean ± SD interval of 20.9 ± 12.6 days. Fifty-six (50.9%) patients had a history of steroid use. Unrelenting ocular or facial pain was the most common presenting symptom, ptosis was the most common anterior segment manifestation, and ophthalmic artery occlusion was the most common posterior segment manifestation. Conclusion: Our data from eastern India reinforces the relationship between COVID-19, diabetes, corticosteroid use, and ROCM. Knowledge of various presenting anterior and posterior segment manifestations of the disease as described in the present study will guide clinicians to recognize the disease early and make every effort to prevent complications.

Central retinal artery occlusion with cilioretinal sparing in a patient with Eisenmenger syndrome.

A young boy in his 20s presented with sudden diminution of vision in right eye 2 days ago. Best-corrected visual acuity was hand movement in right eye and 20/20 in left eye. Funduscopy demonstrated diffuse retinal opacification and swelling at the posterior pole with a cherry red spot at the macula. There was sparing of the superonasal macula with a patent cilioretinal artery. OCT showed diffuse inner retinal thickening of the temporal macula. He was diagnosed as central retinal artery occlusion with cilioretinal sparing in right eye. He was a known case of Eisenmenger syndrome secondary to a large congenital ventricular septal defect. Medical history was notable for prominent pulmonary hypertension and shortness of breath on exertion. Physical examination revealed a harsh systolic murmur. Extremities showed digital erythema and severe clubbing. Chest X-ray demonstrated cardiomegaly. Laboratory examination revealed haemoglobin-220 g/L, haematocrit-60%, serum iron-20 µg/dL.

Surgical Management and Recent Advances in Chemical Injury: A 5-year Review.

PURPOSE: To review the surgical management options in ocular chemical burn, including newer advances. METHODS: Online literature search of published articles over last 5 years on surgical management of ocular chemical burn and newer advances were performed on December 30, 2020. RESULTS: Following literature search and screening using adequate filters, 67 review articles on surgical management of ocular chemical burns were retrieved. The review talks about the surgical management options starting from Debridement in acute stage to various visual rehabilitative procedures in the chronic stage. The review also highlights the evolving surgical advances in this field. CONCLUSION: It is imperative to choose adequate surgical tool wherever applicable; current review discusses the role of each surgical option at different clinical stages in detail.

Transcutaneous retrobulbar amphotericin-B (TRAMB) injection in orbital mucormycosis.

We aim to highlight the role of transcutaneous retrobulbar amphotericin-B (TRAMB) in cases of rhino-orbital mucormycosis. With the COVID-19 pandemic a rapid surge in the number of cases of rhino-orbital mucormycosis has been noted. The gold standard treatment for the progressive orbital disease is exenteration; however, organ salvage should be attempted, when possible. Here comes the role of TRAMB injection. We present a case of a man in his 70s, a known diabetic, who recovered from COVID-19 pneumonia but developed left-sided axial proptosis with orbital apex syndrome and ophthalmic artery occlusion secondary to rhino-orbital mucormycosis. The patient underwent debridement of paranasal sinuses and received intravenous liposomal amphotericin-B and three TRAMB injections. After three TRAMB injections significant improvement in extraocular movements, proptosis and ptosis was noted. An early intervention in orbital disease can avert a more radical procedure.

Severe Paradoxical Manifestations in an Immunocompetent Young Female With Tuberculous Meningitis.

A paradoxical reaction, in patients with tuberculous meningitis, is described as either worsening of pre-existing tuberculous lesions or the appearance of new tuberculous lesions after initial improvement with anti-tuberculosis treatment. The condition is often difficult to predict. When severe, it may also result in considerable neurological morbidity and even death. We aim to report such a rare case of severe paradoxical response in a young female with tuberculous meningitis. An 18-year-old female developed severe headache, vomiting, altered sensorium, decreased vision, and paraparesis. She was on anti-tuberculosis treatment (ATT) for tuberculous meningitis for the past two months. Radiological findings revealed tuberculomas in the left cerebral and cerebellar hemispheres, adhesive arachnoiditis in the cervical spine, and moderate communicating hydrocephalus. Visual evoked potential tests provided electrophysiological evidence of optic neuropathy in the left eye. The appearance of new (tuberculoma and adhesive arachnoiditis in the cervical spine), as well as aggravation of pre-existing tuberculous lesions (worsened hydrocephalus and worsened clinical features), were evident in the patient, suggestive of severe paradoxical response (with HIV negative serology). The patient was treated with corticosteroids, and antibiotics, and continued the ATT programme in a conservative manner. Nonetheless, as the patient had severe CNS manifestations, severe disabilities (poor vision, paraparesis, or quadriparesis) and fatalities were inevitable. Notwithstanding, it is crucial to recognize the paradoxical manifestations of tuberculous meningitis to avoid misleading diagnoses and unwarranted management strategies.

Conjunctival congestion: a novel clinical sign in older children with Tetralogy of Fallot.

Tetralogy of Fallot is the most common cyanotic heart disease in children. While doing echocardiographic examination of children with Tetralogy of Fallot, we observed that many older children with this condition had congestion in their bulbar conjunctiva, easily recognizable even from some distance. This observation led us to design and perform a research study in order to find out the presence of conjunctival congestion in children with Tetralogy of Fallot. 85% of children in the ≥ 5-years of age group had conjunctival congestion without any ocular symptom. This novel clinical finding can act as an adjunct clinical sign for recognizing Tetralogy of Fallot in older children.

Role of amniotic membrane transplantation in treating acute ocular manifestations in Steven-Johnson syndrome and its long-term impact.

Background: Steven-Johnson syndrome (SJS) is a serious disorder affecting the skin and mucous membrane, causing multiple flaccid bullae and purpuric rashes with sheet-like epithelial detachment including the ocular surface. The long-term outcomes following SJS are dismal and manifest as corneal vascularization, lid-wiper keratopathy, and severe dry eyes. The disease course can be modified if amniotic membrane graft is performed at the first week of disease, and the above-said complications can be avoided. This procedure thus not only decreases the morbidity but also improves the quality of life. Purpose: This video discusses the long-term sequelae of SJS which can be modified with timely intervention during the acute stage and thus significantly decreases morbidity. Synopsis: The video demonstrates the simple technique of amniotic membrane transplantation in the acute stage in SJS and its impact in long run. Highlights: There should be a low threshold for doing early amniotic membrane transplantation in patients with SJS with ocular surface involvement. Early intervention can change the disease course and decrease disease morbidity significantly. Video link: https://youtu.be/qgIiVcW56Oo.