Gerassimos Lascaratos

Intravitreal therapy for neovascular age-related macular degeneration and inter-individual variations in vitreous pharmacokinetics

This article aims to provide an interpretation and perspective on current concepts and recent literature regarding the evidence for individualizing intravitreal therapy (IVT), particularly considering iatrogenic and patient factors in the management of neovascular age-related macular degeneration (AMD). As ocular parameters that govern IVT pharmacokinetics do vary between individuals with AMD, developing a personalized strategy could improve safety and efficacy. This has to be derived from clinical measurements and data from laboratory animals; however, it is recognized that the animal models used in the development of intraocular formulations differ in their vitreous geometry from humans. These factors may be of relevance to the design of ophthalmic formulations and optimizing treatment outcomes in AMD. Further studies are needed to drive improvements in clinical practice which are aimed at maximizing the efficacy profile in IVT for AMD by a more rigorous evaluation of patient and surgeon-related variables.

The role of retinal regulation of sleep in health and disease

The process of photoentrainment, through the activation of photoreceptor transduction cascades, influences the circadian physiology of many life forms from primitive invertebrates to primates. In humans, a population of intrinsically photosensitive retinal ganglion cells (ipRGCs) is responsible for mediating the circadian rhythm and is susceptible to primary dysfunction affecting this cell population specifically, or disorders influencing light activation of retinal ganglion photoreceptors. The former may arise through cell depletion in conditions such as inherited or acquired optic neuropathies or conditions like Parkinsons disease which may alter retinal dopamine-mediated neurotransmission, and the latter, secondary to common causes of light transmission reduction associated with ageing and cataract. This review examines the current evidence linking ocular pathology and the resultant reduction in retinal phototransduction with circadian disturbances and sleep disorders, with downstream effects on our overall physiological integrity. As our understanding of the effects of light pathways on circadian biology develops, therapeutic modalities based upon the underlying pathophysiological processes are emerging, although the direct measurement, consequences and treatment of relative or absolute ipRGC dysfunction remain to be fully and clearly elucidated in man.

Nystagmus and reduced visual acuity secondary to drug exposure in utero: long-term follow-up.

PURPOSEnTo investigate nystagmus and other visual system abnormalities among children exposed to opiates and benzodiazepines in utero.nnnMETHODSnRetrospective case series comprising clinical examination and case note review of 25 children with nystagmus and reduced vision who were exposed to controlled drugs during pregnancy.nnnRESULTSnTwenty-four children were exposed to opiates, of whom 13 were also exposed to diazepam. One child was exposed to diazepam alone. All children had horizontal nystagmus, which was either fine pendular or jerk type. The nystagmus had a latent element in 4 children and 8 adopted a compensatory head posture. Where the time of onset of nystagmus was known, it was always prior to 6 months of age. At least 9 children (36%) had delayed visual maturation. The mean initial logarithm of the minimum angle of resolution binocular best-corrected visual acuity (BCVA) was 0.54 at an average of 22 months of age. Thirteen children were followed up for 6 months or longer and their BCVA improved to 0.4 at an average age of 48 months. The nystagmus was clinically improved in only 5 patients. Electroretinogram testing was normal in the 4 children tested. The only ocular structural abnormality was binocular optic nerve hypoplasia in 2 children.nnnCONCLUSIONnExposure to opiates and benzodiazepines in utero may be associated with permanent nystagmus and reduced visual acuity. This is most likely the result of insult(s) to the central nervous system rather than the eyes.

Retinal nerve fiber layer thickness and cognitive ability in older people: the Lothian Birth Cohort 1936 study.

BackgroundThis study aims to examine the relationship between the retinal nerve fiber layer (RNFL) thickness as measured by optical coherence tomography (OCT) and lifetime cognitive change in healthy older people.MethodsIn a narrow-age sample population from the Lothian Birth Cohort 1936 who were all aged approximately 72 years when tested, participants underwent RNFL measurements using OCT. General linear modeling was used to calculate the effect of RNFL thickness on three domains; general cognitive ability (g-factor), general processing speed (g-speed) and general memory ability (g-memory) using age at time of assessment and gender as co-variates.ResultsOf 105 participants, 96 completed OCT scans that were of suitable quality for assessment were analyzed. Using age and gender as covariates, we found only one significant association, between the inferior area RNFL thickness and g-speed (pu2009=u20090.049, η2u2009=u20090.045). Interestingly, when we included age 11 IQ as a covariate in addition to age and gender, there were several statistically significant associations (pu2009=u20090.029 to 0.048, η2u2009=u20090.00 to 0.059) in a negative direction; decreasing scores on measures of g-factor and g-speed were associated with increasing RNFL thickness (ru2009=u2009−0.229 to −0.243, pu2009<u20090.05). No significant associations were found between RNFL thickness and g-memory ability. When we considered the number of years of education as a covariate, we found no significant associations between the RNFL thickness and cognitive scores.ConclusionsIn a community dwelling cohort of healthy older people, increased RNFL thickness appeared to be associated with lower general processing speed and lower general cognitive ability when age 11 IQ scores were included as a covariate.

evaluation of the effect of intravitreal ranibizumab injections in patients with neovascular age related macular degeneration on retinal nerve fiber layer thickness using optical coherence tomography

Purpose To evaluate the effect of repeated intravitreal ranibizumab injections for neovascular age related macular degeneration (nAMD) on the retinal nerve fiber layer (RNFL) thickness using optical coherence tomography. Design A prospective observational cohort study of patients with nAMD. Methods Thirty eyes of 30 patients with nAMD were selected. All patients received three ranibizumab injections and underwent scans using the fast RNFL thickness protocol (Stratus optical coherence tomography) before starting the first injection and 1 month after the third injection. The RNFL thickness measurements prior to the injections and after the third injection were used for the analysis. We also evaluated the effect of the lens status as well as the type of choroidal neovascular membrane on RNFL thickness measurements pre- and post-injection. Pre- and post-injection average and individual quadrant RNFL thickness were measured and statistically analyzed. Results The mean (± standard deviation) pre-injection RNFL thickness was 90.8±18. The mean (± standard deviation) post-injection RNFL thickness was 91.03±15. The pre- and post-injection values of the mean RNFL thickness were not statistically significant. Likewise, the pre- and post-injection values for RNFL thickness in the different quadrants were not statistically significant. There was no statistical significance for the lens status or the type of choroidal neovascular membrane on the RNFL thickness. Conclusion Repeated ranibizumab injections in nAMD appear to have no harmful effect on the RNFL thickness in the short term, in spite of the proven neurotrophic effect of vascular endothelial growth factor. Nevertheless, the safety profile of ranibizumab injections in nAMD needs to be further evaluated in a large multicenter trial with special emphasis on the long-term effects on the retina and optic nerve.

Adams-Oliver syndrome associated with bilateral anterior polar cataracts and optic disk drusen

Adams-Oliver syndrome (AOS) (MIM 100300) was first described in 1945 as a condition of terminal transverse limb defects and aplasia cutis congenita. Since then, its clinical features have been found to be highly variable and include cardiac defects, abdominal wall defects, vascular malformations, brain abnormalities, and ocular anomalies. We report the case of a 3-year-old girl with AOS who was also found to have bilateral anterior polar cataracts and pseudopapilledema secondary to optic disk drusen. To the best of our knowledge, this is the first case of bilateral anterior polar cataracts and pseudopapilledema secondary to optic disk drusen to be reported in association with the AOS.

Outcome of phacoemulsification in previously vitrectomized myopic eyes with axial length greater than 26 mm.

Purpose TO determine the outcome, including the intraoperative and postoperative complications, of phacoemulsification with intraocular lens (IOL) implantation in myopic eyes with axial length of 26 mm or more that had undergone previous pars plana vitrectomy (PPV). Methods This prospective study comprised 37 highly myopic eyes (axial length over 26 mm) with previous vitrectomy that underwent phacoemulsification and were reviewed at a mean postoperative follow-up of 3–6 weeks. The main outcome measures were preoperative and postoperative spherical equivalent, preoperative and postoperative visual acuity, difference between intended and achieved refraction, and any complications during cataract surgery. Results The mean age for cataract surgery was 61.5 years. Nuclear sclerosis was present in 91.89% of patients. The mean axial length was 27.53 mm (range 26.03–30.52 mm). The most common indication for vitrectomy in our study was retinal detachment surgery (35 out of 37). Postoperatively, 34 patients (91.89%) had a visual acuity improvement of 2 or more Snellen lines and the best-corrected visual acuity at final refraction was 6/9 (0.2 logMAR) or better in 30 patients (81.08%). Two patients had perioperative complications (5.4%). Conclusions Cataract surgery with IOL implantation can be performed safely in highly myopic eyes after PPV and the final visual acuity outcomes appear to be dependent on the preoperative status of the retina. Our study suggests that the incidence of intraoperative and postoperative complications can be reduced to a minimum with proper planning and meticulous attention to detail during cataract surgery.

Alcoholic liver disease and bilateral multifocal central serous retinopathy: a case report

IntroductionWe present a unique case of a patient with bilateral, multifocal central serous retinopathy in a patient with alcoholic liver disease.Case presentationA 58-year-old Caucasian man with alcoholic liver disease, liver cirrhosis and ascites presented to the eye clinic. The ophthalmoscopic examination of both eyes revealed a symmetrical pattern of variably sized, slightly yellowish, translucent, raised lesions throughout the fundi which were confirmed to be caused by multifocal central serous retinopathy after optical coherence tomography and autofluoresence tests.ConclusionThis case highlights the possible link between central serous retinopathy and end-stage liver disease, with potential implications for the pathogenesis of central serous retinopathy in these patients.

Myofibroma of the conjunctiva invading the cornea in infancy.

The authors report a novel case of solitary infantile myofibroma originating from the conjunctiva and encroaching over the limbus. This is an observational case report with clinicopathologic correlation. Immunostaining of the lesion was positive for vimentin and smooth muscle actin, and negative for pancytokeratin, desmin, myogenin, EMA, myoglobin, HMB45, and MelanA. To the authors knowledge, this is the first reported case of myofibroma originating from the conjunctiva and this case highlights the importance of considering myofibromatosis in the differential diagnosis of unusual conjunctival lesions.

Accelerated diabetic retinopathy and late human immunodeficiency virus diagnosis.

PURPOSEnTo describe a case of rapidly progressive diabetic retinopathy in a patient who is human immunodeficiency virus positive.nnnMETHODSnThis is an observational case report.nnnRESULTSnFundus examination shows worsening of diabetic retinopathy with new vessels and vitreous hemorrhage in both eyes despite intense pan retinal photocoagulation.nnnCONCLUSIONnFor patients with diabetes, additional diagnosis of human immunodeficiency virus increases the challenge of managing diabetic retinopathy as proliferation can appear rapidly and tends to worsen in these patients.