Ramesh Murthy

Phenotypic characterization of retinoblastoma for the presence of putative cancer stem-like cell markers by flow cytometry.

PURPOSEnRetinoblastoma (Rb) is an intraocular tumor that grows rapidly and poses a threat to sight and life. Similar to other tumors, there is increasing speculation that the Rb tumor also contains cancer stem-like cells that could influence the prognosis and response to therapy. This study was undertaken in an attempt to identify putative stem-like cells by characterizing different subpopulations of cells in retinoblastoma.nnnMETHODSnFreshly isolated tumor cells obtained from unfixed eye specimens (n=7) were analyzed for the presence of CD44, ABCG2, CXCR4, CD133, and CD90 using flow cytometry. RT-PCR was performed to analyze the expression of human Syntaxin1A, PROX1, CD133, and NSE in the sorted subpopulation of tumor cells.nnnRESULTSnTwo different subpopulations of cells were observed in seven samples. The small cells, assigned FSC(lo)/SSC(lo) (forward scatter low/side scatter low, ranging from 1.7% to 17.7%) were characterized as positive for CD44 and negative for CD133, CXCR4, and CD90. The large cells were designated as FSC(hi)/SSC(lo) (ranging from 2.7% to 35.1%) and characterized as positive for all markers. RT-PCR analysis revealed that sorted cells of FSC(lo)/SSC(lo) subpopulation expressed the retinal progenitor cell markers PROX1 and Syntaxin1A.nnnCONCLUSIONSnRetinoblastoma, on flow cytometric analysis, revealed two distinct subpopulations with variable expression of stem cell and retinal progenitor markers. In these populations, the FSC(lo)/SSC(lo) subpopulation appeared to be more primitive, since they expressed stem cell (CD44) and retinal progenitor markers (PROX1 and Syntaxin 1A) combined with a relatively lower percentage of differentiated markers. Moreover, the FSC(hi)/SSC(lo) subpopulation showed a higher percentage of differentiated markers (CD90 and CD133).

Extramedullary leukemia in children presenting with proptosis

BackgroundWe highlight the orbital manifestations of acute myeloid leukemia and the role of peripheral blood smear in the diagnosis of these cases. A total of 12 patients who presented with proptosis and were subsequently diagnosed to have acute myeloid leukemia based on incision biopsy or peripheral blood smear were included in the study.ResultsA retrospective review of all cases of acute myeloid leukemia presenting to the Orbital clinic was performed. The age at presentation, gender, presenting features, duration of symptoms and fundus features were noted. In addition the temporal relationship of the orbital disease to the diagnosis of leukemia, laterality, location of the orbital mass, imaging features and the diagnostic tools used to diagnose leukemia were noted. The median age at presentation was 6 years. The male: female ratio was 0.7:1. None of these patients had been diagnosed earlier as having acute myeloid leukemia. The presenting features included proptosis in all patients, orbital mass in 5 (41.7%), visual symptoms in 2 (16.7%) and subconjunctival hemorrhage in one patient (8.3%). A diagnosis of acute myeloid leukemia was established by incision biopsy in 4 patients, subsequently confirmed by peripheral blood smear testing and bone marrow biopsy in 2 patients which revealed the presence of systemic involvement. Imprint smears of the biopsy identified blasts in 2 of 4 cases. In 8 patients presenting with ocular manifestations, diagnosis was established by peripheral blood smear examination alone which revealed a diagnosis of acute myeloid leukemia.ConclusionA peripheral blood smear should be performed in all cases of sudden onset proptosis or an orbital mass in children and young adults along with an orbital biopsy. It can always be complemented with a bone marrow biopsy especially in cases of aleukemic leukemia or when the blood smear is inconclusive.

Bilateral multiple extraocular muscle metastasis from breast carcinoma.

We report a rare presentation of an initially misdiagnosed case of a pseudotumor, which on histopathology was diagnosed as bilateral breast metastases of lobular carcinoma involving multiple extraocular muscles. A 61-year-old lady presented with external ophthalmoplegia and diplopia. Incisional biopsy was performed using a lid crease approach and the patient received radiotherapy and hormonal therapy. Following prolonged hormonal therapy, complete remission was achieved, with improvement in ocular motility and resolution of diplopia, about 18 months after the initial presentation. Multiple extraocular muscle involvement by breast carcinoma metastasis is very rare and should be considered in the differential diagnosis, especially in patients with a prior history of breast carcinoma.

Botulinum toxin in ophthalmic plastic surgery.

Botulinum toxin chemodenervation has evolved greatly over the past 30 years since its introduction in the 1970s for the management of strabismus. Among ophthalmic plastic surgeons, botulinum toxins are often used as the first line treatment for facial dystonias. These toxins are also efficacious for the temporary management of various other conditions including keratopathies (through so called chemo-tarsorraphy), upper eyelid retraction, orbicularis overaction-induced lower eyelid entropion, gustatory epiphora, Freys syndrome, and dynamic facial rhytids such as lateral canthal wrinkles (crows feet), glabellar creases and horizontal forehead lines. This article describes the pharmacology, reconstitution techniques and common current applications of botulinum toxins in ophthalmic plastic surgery.

Acquired cyclic exotropia and hypotropia.

Cyclic exotropia, a very rare condition, consists of periods of exotropia and orthotropia alternating on a regular, most commonly 48-hour, cycle. Cyclic vertical deviations, including cyclic oculomotor nerve palsy, also are extremely uncommon. Cyclic esotropia, which is more common than cyclic exotropia, has been reported to occur more frequently in children than adults. We describe an adult patient who developed cyclic exotropia and hypotropia associated with monocular loss of vision.

Custom Ocular Prosthesis in Children: How Often is a Change Required?

Purpose: To evaluate the indications, outcome and replacement schedule of custom ocular prostheses (COP) in children. Methods:Retrospective review evaluating indications, outcome and replacement schedule of COP in children (≤16 years). Results:Three hundred and thirty (330) children were fitted with COP. With average follow-up of 18.05 months (range 1-50 months), 136(41.2%) children needed replacement/modification of the prosthesis. Information regarding indications for replacement/modification of prosthesis was available in 125 cases. Indications included enophthalmic prosthesis in 34(27.2%), prosthesis rotation within the socket in 25(20%), loose fit in 16(12.8%), decentration of the cornea in 15(12%), color touch up in 13(10.4%), lost prosthesis in 8(6.4%), cosmetically significant ptosis in 2(1.6%), replacement following implant exchange surgery in 2(1.6%) and combination of above factors in 10(8%). Time for replacement/modification of prosthesis was assessed in 3 age groups. In ≤3 years, 47% (36 out of 76) children underwent replacement/modification at a mean duration of 18 months (range 3–39 months) from the date of prosthesis fitting. In the 3–12 years age group, 43% (80 out of 184) underwent replacement/modification at 21 months (range 2–48 months); and in the 12–16 year age group, 29% (20 out of 70) underwent replacement/modification of prosthesis at a mean duration of 26 months (range 3-50 months). Conclusion: A change of prosthesis is required between 18-26 months following prosthesis placement in children.Over an average of 18 months, a change in the prosthesis was required in 41%, with the youngest age group having the highest exchange rate (47%), and the oldest group the lowest (29%).

PHACE Syndrome Associated With Congenital Oculomotor Nerve Palsy

PHACE syndrome is a multisystem disorder presenting with facial hemangiomas, arterial anomalies, cardiac anomalies, posterior fossa malformations and eye abnormalities. The eye abnormalities include microphthalmos, cataracts, optic atrophy and iris hypoplasia. Amongst the neurological anomalies, posterior fossa malformations are common. Fourth nerve palsy has been reported with PHACE syndrome. We report a child presenting with a triad of congenital third nerve palsy, cerebellar hypoplasia and facial capillary hemangioma.

Lateral fixation of sclera to the periosteum with medial rectus disinsertion for severe myopic strabismus fixus

Myopic strabismus fixus is characterized by severe ocular motility restriction with the development of progressive esotropia and hypotropia. Management of severe cases with strongly positive forced duction test can be challenging. We describe a longstanding case of myopic strabismus fixus, which was managed by bilateral medial rectus disinsertion and scleral fixation laterally to the periosteum.

Bilateral choroidal osteoma with optic atrophy

Choroidal osteoma is a rare, yellowish-white lesion of the choroid that predominantly affects young women in the second decade of life. Subretinal neovascularization or collection of subretinal fluid may occur in 50 % or more patients in the long run. A 15-year-old girl presented to our practice with bilateral choroidal osteoma associated with advanced bilateral optic atrophy. The underlying cause for optic atrophy is unclear; possible explanations include mechanical pressure effect and ischemic damage.

Centurion Syndrome: Clinical Presentation and Surgical Outcome

ABSTRACT Purpose: To describe the clinical signs and outcome of surgery in cases with Centurion syndrome and highlight the clinical presentation of this syndrome. Methods: A retrospective review of records of patients with Centurion syndrome who underwent surgery between January 2002 and July 2007. The position of the punctum, nasal bridge prominence, Hertel exophthalmometry and the presence of inferiorly directed sharp angulation of the medial canthus was noted. The patients underwent anterior canthal tendon release, punctoplasty or medial conjunctivoplasty or a combination of these. Results: Of the 13 cases, 10 had been treated medically elsewhere. The mean age of onset was 20.7 years. Most of the patients were male 10 (76.9%). A prominent nasal bridge was demonstrable in 9 (69.2%) patients and sharp inferior angulation of the medial canthus, the ‘beak’ sign was present in 9 (69.2%) cases. Anterior canthal tendon release alone was performed in 4 patients, in combination with punctoplasty in 5 and with conjunctivoplasty in 4. Watering resolved in 10 patients. 3 patients who had a combination of anterior canthal tendon release and punctoplasty had persistent but asymptomatic epiphora. Discussion: Centurion syndrome is characterised by the abnormal anterior insertion of the medial canthal tendon with displacement of the punctum out of the lacrimal lake. Most cases present with unexplained watering. Surgical management by anterior canthal tendon release with or without conjunctivoplasty or lower lid retractor plication is usually successful.