Rustum Karanjia

Electrophysiological effects of intravitreal Avastin (bevacizumab) in the treatment of exudative age-related macular degeneration

Objective: To examine the sensitivity of the multifocal electroretinogram (mf-ERG) at measuring changes in retinal electrical activity in response to Avastin (bevacizumab) treatment for age-related macular degeneration (ARMD). Methods: Nine subjects with exudative ARMD, not previously treated with bevacizumab in the investigated eye, underwent pretreatment testing with mf-ERG and intravenous fluorescein angiography (IVFA). A second mf-ERG test was conducted post-treatment. The P1 response amplitudes were examined for the hexagons corresponding to areas of pathology on the IVFA. Intertest variability was accounted for by examining areas without pathology. Aggregate responses were also generated for central and lesion-associated responses. Results: Changes in P1 response amplitude correlated with changes in visual acuity (R2>0.96). An improvement in Snellen visual acuity correlated with a significant improvement in P1 response amplitude from lesion associated recordings (p<0.03). Changes in P1 response amplitudes were not observed when aggregate responses were generated. Conclusion: This study represents a novel method for assessing an improvement of mf-ERG responses. This is the first study to demonstrate a statistically significant change in retinal electrical activity postbevacizumab in patients with ARMD. This study demonstrates a method for utilising mf-ERG to assess changes in retinal electrical activity and to assess the effectiveness of treatments such as bevacizumab.

Natural History of Conversion of Leber's Hereditary Optic Neuropathy: A Prospective Case Series

PURPOSE To illustrate the natural history of Lebers hereditary optic neuropathy (LHON). DESIGN Prospective observational case series. PARTICIPANTS The Soave-Brazil pedigree of m.11778G>A/ND4 mitochondrial DNA LHON mutation. METHODS A prospectively acquired database of the Soave-Brazil pedigree was reviewed. Data from 285 individuals were included in the database over a 15-year period. The pedigree was reviewed for unaffected mutation carriers who converted to affected status, 6 patients with LHON were identified. The medical records were reviewed 1 year preconversion to 1 year postconversion for visual acuity (logarithm of the minimum angle of resolution [logMAR]), Humphrey Visual Field (HVF) mean deviation (MD), and retinal nerve fiber layer (RNFL) thickness, as measured by Cirrus (Carl Zeiss, Oberkochen, Germany) optic coherence tomography (OCT). The RNFL thickness values were normalized for age. Visual acuity, HVF, and processed RNFL data from each of the 12 eyes were then sorted into 2-month time periods relative to the date of conversion, within which they were averaged. MAIN OUTCOME MEASURES The main outcome measures were visual acuity, HVF MD, and RNFL thickness. RESULTS Decreased visual acuity preceded conversion by up to 2 months and then declined up to 8 months postconversion. Decrease in HVF MD occurred at least 4 months preceding conversion, after which values decreased until plateau at 6 to 8 months. Average RNFL thickness was above normal baseline thickness in all 4 quadrants as measured by OCT at the time of conversion. Increase in RNFL thickness preceded conversion as early as 4 to 6 months, peaked at conversion, and decreased until individual plateaus. The temporal quadrant was first to be involved, then the inferior and superior quadrants, and the nasal quadrant showed the latest and least changes. CONCLUSIONS Subclinical changes preceded the date of conversion and may reflect the complicated nature of identifying the date of conversion in LHON. Early increases in RNFL preceding conversion suggest that structural changes precede clinically significant vision loss. Asynchronous quadrant involvement supports a previously published mathematical model. The natural history of LHON is not a subacute process, as previously believed, but progresses more slowly, taking up to 8 months to plateau.

Optimization of Visual Evoked Potential (VEP) Recording Systems

OBJECTIVE To explore the influence of environmental conditions on pattern visual evoked potential (VEP) recordings. METHODS Fourteen subjects with no known ocular pathology were recruited for the study. In an attempt to optimize the recording conditions, VEP recordings were performed in both the seated and recumbent positions. Comparisons were made between recordings using either LCD or CRT displays and recordings obtained in silence or with quiet background music. Paired recordings (in which only one variable was changed) were analyzed for changes in P100 latency, RMS noise, and variability. RESULTS Baseline RMS noise demonstrated a significant decrease in the variability during the first 50msec accompanied by a 73% decrease in recording time for recumbent position when compared to the seated position (p<0.05). Visual evoked potentials recorded using LCD monitors demonstrated a significant increase in the P100 latency when compared to CRT recordings in the same subjects. The addition of background music did not affect the amount of RMS noise during the first 50msec of the recordings. CONCLUSION This study demonstrates that the use of the recumbent position increases patient comfort and improves the signal to noise ratio. In contrast, the addition of background music to relax the patient did not improve the recording signal. Furthermore, the study illustrates the importance of avoiding low-contrast visual stimulation patterns obtained with LCD as they lead to higher latencies resulting in false positive recordings. These findings are important when establishing or modifying a pattern VEP recording protocol.

Bilateral acute angle closure glaucoma associated with hydrochlorothiazide-induced hyponatraemia

We report a case of a 67-year-old woman presenting with bilateral acute angle closure. On investigation, she was found to have bilateral ciliary effusions and profound hyponatraemia. Her effusions resolved with the cessation of hydrochlorothiazide and normalisation of her blood sodium levels by fluid restriction. This case displays a novel association of hyponatraemia as a possible mechanism for the development of bilateral acute angle closure.

Electroretinograms and Normative Data

Electroretinography (ERG) is an important clinical tool that provides an objective quantitative measure of retinal function. Decreased a and b wave amplitudes and prolonged latencies correlate to reductions in retinal function that may be the result of toxicity, ischemic damage, or retinal dystrophy (Fishman et al. 2001, Ophthalmology monographs). Furthermore, since the different components of the ERG waveform correspond to the different layers of the retina, one is able to attribute changes in the ERG to damage to specific retinal layers. This data can be a useful surrogate for retinal health, for example establishing safety profiles for drugs under clinical development. Since 1989 the International Society for Clinical Electrophysiology of Vision (ISCEV) has provided standards for the recording of ERGs. These documents provide a framework for the clinical electrophyisologist to obtain “standard” ERG recordings (Marmor 1989). The variety of permissible ERG instruments and their individual calibration requirements contributes to significant inter-laboratory variability. This variability is recognized in the ISCEV standards and partly addressed by stating “it is incumbent on the manufactures and users to verify that full-field stimulation meets the requirements of this standard.” Placing the onus for compliance on the manufactures but leaving the clinical electrophyisologist to determine if the recording standards are indeed met. ERG standards have extended beyond the aand b-wave of the full field flash ERG. The pattern ERG (PERG) is the electroretinal response to a pattern reversing stimulus such as bar gratings or checkerboard pattern. The PERG primarily reflects ganglion cell function and since it is viewed on display monitors it largely represents ganglion cell function within the macula. The peak and trough components of the PERG have been formally defined as the N35, P50 and N95 which represent the polarity (Negativity or Positivity) and the mean latency of occurrence. The ISCEV has produced standards for the recording and reporting of the PERG (Holder et al. 2007). While the PERG provides a single waveform which represents the electroretinal response of the entire macular region, the clinical multifocal electroretinogram (mERG) provides information of local retinal function. The mERG is recorded typically displaying the local retinal response of 61 or 103 local regions within the central 45 of the posterior pole. The responses represent localized cone-driven ERGs obtained in the light adapted state. While the waveform morphology of the mERG is similar to the fullfield ERG the electroretinal

Macular choroidal osteoma with progressive widespread outer-retinal dysfunction

Typically, choroidal osteoma is a unilateral, juxtapapillary tumour found in women in their second or third decades. Patients can present with metamorphopsia, blurred vision, and visual field defects, butmost are asymptomatic. Gradual visual loss is typically associated with degeneration of the overlying retinal pigment epithelium (RPE). Acute visual loss and (or) metamorphopsia is typically associated with hemorrhagic subretinal fluid accumulation from an associated choroidal neovascular membrane. A 49-year-old male was referred to a tertiary care centre with decreased visual acuity OS and enlargement of an abnormal area of RPE that had been diagnosed as central serous retinopathy 17 years earlier. Best-corrected visual acuity was 6/6 OD and 6/9-2 OS. A slightly elevated, depigmented area was observed superior to the macula (Fig. 1). A subretinal mass extending from the optic nerve head to the foveal avascular zone was identified on optical coherence tomography. CT scan (Fig. 2) revealed a small focal area of calcification involving the submacular choroid, which was corroborated by B-scan. A fluorescein angiogram demonstrated early hyperfluorescence with late staining (Fig. 1). On Goldmann visual field examination, there was a relative scotoma in the right nasal hemifield of the left eye. Microperimetry demonstrated a larger lesion than seen with fundus photography and intravenous fluorescein angiography (Fig. 3). The patient was evaluated at an ocular oncology centre, and the diagnosis of choroidal osteoma was confirmed. The recent decrease in OS visual acuity was presumed to be a result of the mass impinging upon the fovea, and various treatment options were considered. Radiation therapy might have resulted in significant radiation retinopathy and, similarly, transpupillary thermotherapy might have caused further central vision loss. Multifocal electroretinography was performed (Fig. 3). Regional retinal responses within the area overlying the lesion were found to be of similar amplitude when compared with responses within an area of equal eccentricity but without underlying pathology. This was in contrast with the decline in visual acuity and deficits on perimetry testing. Choroidal osteoma is a rare ocular tumour of unknown etiology. Cases of choroidal osteoma in males and children are very rare. Several theories of the pathogenesis have been proposed, including inflammatory, hereditary, and congenital theories. This patient’s history of serous chorioretinopathy may represent a precursor or an early manifestation of the osteoma lesion. This report is the first to illustrate multifocal electroretinography responses overlying a choroidal osteoma. The normal responses suggest that the reduction in visual acuity may be due to the distortion of the retina as opposed to damage of the retina nerve fibre layer. Choroidal osteomas commonly become bilateral, highlighting the need for frequent fluorescein angiography in order to detect any new lesions in the perifoveal region bilaterally. Early detection may allow for the use of a prophylactic barrier line of laser treatment to the advancing edge, which may preserve vision. We continue to follow

Treatment of Leber’s Hereditary Optic Neuropathy

Lebers hereditary optic neuropathy (LHON) is a rare mitochondrial disease of complex I of the respiratory chain. Patients typically present with subacute vision loss in one eye followed by the loss of vision in the second eye approximately 4-8 weeks later, ultimately leading to blindness. Therapeutic interventions have so far failed to prevent this vision loss; however, there has been recent interest in new managements for this prototypic mitochondrial disease. A review of the literature was performed and articles were identified using PubMed (the search terms LHON and treatment were used). These publications were paired to the clinical trials listed on the clinicaltrials.gov website. There are eighteen studies including 5 phase II/III clinical trials in LHON listed on the clinicaltrials.gov website and they vary from oral medication to eye drops and intravitreal injections. In this review, we discuss failed and active therapies and the future of clinical trials in LHON.

Profound vision loss impairs psychological well-being in young and middle-aged individuals

Purpose The aim of this study was to evaluate the effects of profound vision loss on psychological well-being in adolescents, young adults, and middle-aged adults with regard to mood, interpersonal interactions, and career-related goals. In addition, we assessed the significance of the resources that may be used to enhance psychological well-being in cases of profound vision loss, and in particular, examined the utility of low vision aids and the role of the ophthalmologist as a provider of emotional support. Methods A questionnaire was issued to individuals aged 13–65 years with profound vision loss resulting from Leber’s hereditary optic neuropathy (LHON). Depression prevalence was evaluated with questions regarding major depressive disorder symptomatology. Participants appraised the effects of vision loss on their interpersonal interactions and career goals by providing an impact rating (IR) on a 21-point psychometric scale from −10 to +10. Social well-being index was defined as the average of interpersonal IR and career IR. Subjects were additionally asked about the use of low vision aids and sources of emotional support. Results A total of 103 participants (mean age =26.4±11.2 years at LHON diagnosis; mean ± standard deviation) completed the questionnaire. Nearly half (49.5%) met the depression criteria after vision loss. Negative impacts on interpersonal interactions (median IR = −5) and career goals (median IR = −6) were observed; both ratings were worse (P<0.001) for depressed versus nondepressed subjects. Older age at diagnosis corresponded to higher depression prevalence and increased incidence of negative interpersonal IR and career IR. Sixty-eight percent of subjects used electronic vision aids; controlling for age, social well-being index was higher among these individuals than for those who did not use electronic aids (P=0.03). Over half of the participants (52.4%) asserted that they derived emotional support from their ophthalmologist. Conclusion Profound vision loss in adolescents, young adults, and middle-aged adults is associated with significant negative psychological and psychosocial effects, which are influenced by age and use of electronic vision aids. Ophthalmologists, in addition to managing vision loss, may serve an important role in the emotional adaptation of these patients.

Comparison of 2 pupil expansion devices for small-pupil cataract surgery

UNLABELLED We compared the degree of postoperative iris distortion with the diamond-shaped Malyugin ring and the circular Visitec I-Ring iris dilators using postoperative iris photographs in a patient with bilateral small nondilating pupils. Routine phacoemulsification was performed in the right eye with the assistance of a Malyugin ring for iris dilation. One month later, the same procedure was performed in the left eye using the circular ring for iris dilation. Anterior chamber slitlamp photographs were taken of both eyes. The amount of distortion in the postoperative pupils was calculated using the ratio of the postoperative pupil area to the area of the circle of best fit. The circular ring, constructed from a softer material, resulted in 11% distortion and the Malyugin ring, 49%, suggesting that the circular ring caused less trauma to the iris. FINANCIAL DISCLOSURE None of the authors has a financial or proprietary interest in any material or method mentioned.

High Rate of Early Posterior Capsule Opacification following Femtosecond Laser-Assisted Cataract Surgery

Purpose: To compare the rates of rapid posterior capsule opacification (PCO) formation in the first 3 months following femtosecond laser-assisted cataract surgery (FLACS) to manual anterior capsulorhexis. Methods: Retrospective review of 29 cases of FLACS, comparing the rates of PCO in the first 3 months following surgery to 50 consecutive cases of manual anterior capsulorhexis. Results: Seven of the 29 FLACS cases developed PCO requiring capsulotomy at 3 months, while none of the control cases required a capsulotomy over the same time period (p < 0.05). Conclusion: There is an increased incidence of early-onset PCO following the use of femtosecond laser in cataract surgery that is otherwise unfounded in manual capsulorhexis. This suggests that the use of a femtosecond laser could increase the risk of this novel postoperative complication.