Potential pharmacokinetic role of organic cation transporters in modulating the transcorneal penetration of its substrates administered topically.

PURPOSE: We hypothesize organic cation transporters (OCT) may have a potential role in determining the pharmacokinetics and toxicity of organic cation drugs applied topically. Hence, in the present in vivo study, we attempted to evaluate the role of OCT in modulating the transport of its substrates after topical application. METHODS: New Zealand albino rabbits of either sex were used. Transcorneal penetration of OCT substrates tetraethylammonium and metformin after single instillation was evaluated in the absence and presence of OCT blockers (quinidine and atropine). Aqueous humor (AH) samples were collected through paracentesis amounting to 70-100 µl under topical anesthesia at various time intervals. The samples were subjected for estimation of both substrate as well as blocker concentrations using liquid chromatography mass spectrometry. RESULTS: Topical pre-treatment (30 min before substrate) of OCT blockers significantly decreased the transcorneal penetration of OCT substrates after single topical administration. The levels of blockers reaching AH in the presence of substrates were also modulated at 60 min after its administration as compared with its control. CONCLUSION: OCT are functionally active in the uptake of their substrates from tear to AH. Therefore, OCT in the corneal epithelium may be positioned from apical to basolateral. When administering their substrates/blockers topically, both may be competing for OCT for their uptake across the cornea, thereby decreasing the corneal penetration. Hence OCT can have a potential pharmacokinetic role in modulating the ocular bioavailability of their substrates administered topically, which are used as ocular therapeutics.

Inflicted neuro-trauma in infancy.

Two infants with non-accidental inflicted neuro-trauma are reported. One presented with sudden onset lethargy, respiratory difficulty and unexplained seizures. There were bilateral retinal bleeds and extradural hemorrhage. Other was a well thriving child who had 2 seizures and was noted to lack visual fixation. Retinal hemorrhages and chronic subdural and intraparenchymal hemorrhages were subsequently discovered. We highlight the importance of suspecting child abuse in infants with sudden unexplained unresponsiveness, seizures or respiratory difficulty and the unusual occurrence of extradural hemorrhage.

Changing profile of retinopathy of prematurity.

The aim of this study was to determine the evolving trends of retinopathy of prematurity (ROP) at a tertiary neonatal intensive care unit. In an ongoing screening programme for ROP, we estimated the incidence of ROP among at-risk neonates in a tertiary care unit. We compared our data over the last 12 months (1999-2000; period II) to the previously published data (1993-94; period I) to study changes in the spectrum of the disease. The overall incidence of ROP in period II was not significantly different from the incidence in period I (32 vs. 20 per cent, p > 0.05). However, a decreasing trend in the proportion of severe ROP (stage III) from 46 to 21 per cent in the later period was noted. The need for cryotherapy also dropped significantly compared with the earlier period (8 vs. 46 per cent respectively, p < 0.05). On multivariate analysis, apnea (p < 0.001; RR = 12.5; 95 per cent CI, 3.03-50.9; clinical sepsis (p < 0.001; RR = 5.7; 95 per cent CI, 1.6-20.7); and male sex (p < 0.001; RR = 6.3; 95 per cent CI 1.6-25.5) emerged as significant risk factors. Although the incidence of ROP is static, the more severe form of the disease (stage III) is showing a decline. Our data suggests that efficient management of apnea and sepsis may be crucial in further minimizing the risk of ROP.

Phacoemulsification combined with silicone oil removal through a posterior capsulorhexis.

PURPOSE: To evaluate the technique of silicone oil removal through a posterior capsulorhexis combined with phacoemulsification and intraocular lens (IOL) implantation. SETTING: Dr. Rajendra Prasad Center for Ophthalmic Sciences, New Delhi, India. METHODS: Fifteen eyes of 15 patients had phacoemulsification with removal of silicone oil, which had been used for intraocular tamponade after a previous pars plana vitrectomy. Eyes with a stable retina were included in the series. In all eyes, the silicone oil was removed through a planned posterior capsulorhexis after phacoemulsification. The parameters evaluated were the primary diagnosis, duration between silicone oil instillation and phacoemulsification, type of cataract, preoperative and postoperative best corrected visual acuities (BCVAs), and complications such as frequency of retinal redetachment and secondary cataract. RESULTS: Vitreoretinal surgery with silicone oil instillation was performed for rhegmatogenous-tractional detachment resulting from Eales' disease in 6 eyes and from proliferative diabetic retinopathy in 2 eyes, for primary rhegmatogenous retinal detachment in 6 eyes, and for traumatic rhegmatogenous detachment in 1 eye. The mean duration between the silicone oil instillation and phacoemulsification was 7.5 months +/- 3.8 (SD). Fourteen eyes had posterior subcapsular cataract, and 10 had nuclear sclerosis. Preoperative BCVA was worse than 6/60 in all eyes. The BCVA was 6/60 or better in 9 eyes after a minimum follow-up of 6 months. Two eyes had choroidal detachment in the early postoperative period. No eye had vitreous hemorrhage, retinal redetachment, secondary cataract, clinically significant endothelial decompensation or macular edema, or a dislocated IOL. CONCLUSION: The results indicate that silicone oil removal through a posterior capsulorhexis during phacoemulsification is a viable option and can be performed in selected cases of cataract with previous silicone oil instillation and a stable retina.

Contrast sensitivity following focal laser photocoagulation in clinically significant macular oedema due to diabetic retinopathy.

PURPOSE: To evaluate the influence of focal aser photocoagulation on contrast sensitivity in diabetic patients with clinically significant macular oedema (CSMO). METHODS: A prospective non-comparative interventional study was performed on a group of patients with CSMO at Dr Rajendra Prasad Centre for Ophthalmic Sciences, New Delhi, a tertiary eye care centre. Thirteen diabetc patients (14 eyes) with CSMO and no history of prior photocoagulation were recruited for this study. Direct focal photocoagulation of all leaking microaneurysms was performed using an argon green laser (514 nm). A contact lens was used as a slit lamp delivery system. Evaluation of the best corrected Snellen visual acuity, contrast senstivity, slit lamp biomicroscopy, macular status on direct ophthalmoscopy and fluorescein angiography was carried out 1 month and 3 months after laser photocoagulation. RESULTS: Following direct focal laser photocoagulation, focal CSMO resolved completely in all but one eye, 4-8 weeks later, as seen on slit lamp biomicroscopy and/or fluorescein angiography. Post-treatment, visual acuity remained stationary in eight eyes, improved by one line in three eyes, by two lines in two eyes and by three lines in one eye. The mean +/- SD pretreatment and post-treatment decimal visual acuities were 0.49+/-0.30 and 0.59+/-0.28, respectively. The mean +/- SD pre-laser contrast sensitivity score was 121.3+/-83.6, which increased significantly to a mean +/- SD of 151.6+/-80.5 fo lowing direct focal photocoagulation. CONCLUSION: Focal argon laser photocoagulation in CSMO in diabetics helps in improving the contrast sensitivity and stabilizes the visual acuity. The changes in contrast sensitivity and visual acuity are independent of each other.

Suprachoroidal haemorrhage. Secondary management.

We report a case of successful management of expulsive suprachoroidal haemorrhage following cataract surgery. This case study highlights the strategy of adequate management.

Threshold stage of retinopathy of prematurity: maternal and neonatal risk factors.

BACKGROUND: The aim of this study was to review the maternal and neonatal risk factors associated with retinopathy of prematurity (ROP) and the threshold stage of the disease. PATIENTS AND METHODS: In this prospective cohort study, all preterm infants of less than 1501 g birth weight were screened for ROP between January 1996 and December 1997 at the neonatal unit of the Maternity Hospital in Kuwait. The rate of the threshold stage of ROP, as well as risk factors associated with the disease, were identified. RESULTS: A total of 234 babies were screened for ROP, of which 151 (64.5%) developed the disease and 34 (14.5%) had the threshold stage of ROP. Several factors were found to be associated with ROP and threshold ROP. Stepwise regression analysis revealed that low birth weight (P<0.002) and exposure to high oxygen concentration (P<0.0001) were independently associated with ROP. In addition, low birth weight (P<0.006), high oxygen concentration (P<0.003), and culture-proven sepsis (P<0.04) were found to be independent predictors of threshold ROP. CONCLUSION: Apart from low birth weight and exposure to high oxygen therapy, which are well-documented risk factors of ROP, septicemia was also found to be associated with the threshold stage of ROP.

Modified needle drainage of subretinal fluid for conventional scleral buckling procedures.

This study evaluated the efficacy and safety of a new technique used to drain subretinal fluid (SRF) during conventional scleral buckling procedures. The procedure was performed on 15 patients with primary rhegmatogenous retinal detachment in whom drainage of SRF was necessary during the surgery. It was successful in all but 1 case. The only significant complication was subretinal hemorrhage from the punctured choroid in 1 case, which resolved spontaneously without subsequent complications. This technique reduced the risk of complications during external SRF drainage, especially retinal and vitreous incarceration.

Topical atropine and timolol therapy in failed retinal detachment surgery.

We conducted a double-blind randomized prospective study to evaluate the efficacy of topical timolol alone and topical timolol and atropine combined in cases of operated failed retinal detachment surgery cases in which no apparent open break explained the surgical failure. In both groups with and without proliferative vitreoretinopathy no statistically significant difference in retinal reattachment was found.

Unusual retinal manifestation in a combination of Sturge-Weber and Klipplel-Trenaunay syndrome--a case report.

An unusual retinal manifestation of arteriovenous communications is reported in a case showing a combination of Sturge-Weber and Kippel-Trenaunay syndromes. The arteriovenous communications are thought to be similar to those seen in the limbs in Parkes-Weber syndrome. This retinal finding indicates that the three syndromes are intricately related to each other and may be an incomplete manifestation of a single pathophysiologic entity which may be named neurocutaneous angiomatosis.

Subretinal fluid in the diagnosis of posterior scleritis.

The etiology of subretinal mass lesions is very difficult to establish. A 28-year-old man presented to us with an area of choroiditis, which progressed, despite corticosteroid and antibiotic therapy, to an exudative retinal detachment, secondary glaucoma and a painful blind eye. To develop a means of identifying the cause of such lesions, we did a subretinal fluid tap prior to enucleation. Cytopathology showed only inflammatory cells and the final histopathological diagnosis was that of a granulomatous scleritis.