Determination of the Trans-Lamina Cribrosa Pressure Difference in a Community-Based Population and its Association with Open-Angle Glaucoma.

PURPOSE: To determine the trans-lamina cribrosa pressure difference (TLCPD) in a cohort of normal community-based patients and the relationship to primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG). DESIGN: Retrospective cohort study of the Mayo Clinic Study of Aging. PARTICIPANTS: The Mayo Clinic Study of Aging is a prospective study evaluating the normal aging population. METHODS: Mayo Clinic Study of Aging patients who underwent routine lumbar puncture (LP) studies with eye examinations were reviewed. The trans-lamina cribrosa pressure difference was calculated in 2 contexts of intraocular pressure (IOP): (1) maximum IOP at eye visit closest in time to the LP (closest-in-time TLCPD); and (2) IOP before IOP-lowering treatment (pretreatment IOP and pretreatment TLCPD) in POAG and NTG patients. Glaucoma patients without POAG or NTG were excluded. Regression analyses were performed to determine the relationship with glaucoma. MAIN OUTCOME MEASURES: IOP, intracranial pressure, TLCPD, POAG, normal-tension glaucoma (NTG) diagnosis, glaucoma parameters. RESULTS: Five hundred forty-eight patients were analyzed. Of these, there were 38 treated glaucoma patients (14 POAG and 24 NTG) and 510 nonglaucomatous patients. Cerebral spinal fluid (CSF) opening pressure was 155.0 ± 42.2 mmH2O in nonglaucomatous patients, 144.0 ± 34.0 mmH2O in POAG (P = 0.15 vs. nonglaucomatous patients), and 136.6 ± 29.3 mmH2O in NTG (P = 0.017 vs. nonglaucomatous patients). Intraocular pressure was 15.47 ± 2.9 mmHg in nonglaucomatous patients, 26.6 ± 3.7 mmHg in POAG, and 17.4 ± 3.4 mmHg in NTG. The closest-in-time TLCPD in the nonglaucomatous cohort was 4.07 ± 4.22 mmHg, which was lower than both the POAG cohort (7.19 ± 3.6 mmHg) and the NTG cohort (5.79 ± 4.5 mmHg, P = 0.04). Pretreatment TLCPD for the overall glaucoma cohort was 10.57 ± 6.1 mmHg. The POAG cohort had a higher pretreatment TLCPD (16.05 ± 5.2 mmHg) than the NTG cohort (7.37 ± 4.1 mmHg; P < 0.0001). Closest-in-time TLCPD for the nonglaucoma cohort (4.07± 4.2 mmHg) was significantly lower than pretreatment TLCPDs for both POAG (16.05 ± 5.2 mmHg; P < 0.0001) and NTG (7.37 ± 4.1 mmHg; P < 0.0001) cohorts. CONCLUSIONS: This study establishes the baseline TLCPD in a large cohort of normal, community-based patients. The differences in regression analysis between TLCPD and IOP suggests NTG pathophysiology is partially driven by TLCPD, but is also likely multifactorial. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Escape from prism.

A 14-year-old boy with a history of shunted congenital hydrocephalus began having headaches with nausea and vomiting after transcontinental flights. He gradually developed horizontal diplopia indicative of mild bilateral sixth nerve palsy, without papilledema or ventriculomegaly. Intracranial pressure monitoring showed no signs of elevation. After he subsequently developed papilledema, surgical exploration showed shunt malfunction, and shunt replacement produced rapid resolution of symptoms. This case demonstrates the importance of relying on clinical history and neuro-ophthalmologic examination in patients with hydrocephalus and suspected shunt failure, even when objective confirmatory evidence of intracranial pressure elevation is lacking.

Use of sweep visual evoked potential in preverbal children with optic nerve hypoplasia.

PURPOSE: To evaluate sweep VEP (sVEP) in preverbal children with optic nerve hypoplasia (ONH) and to assess associations between sVEP results, patient clinical characteristics and future recognition visual acuity. METHODS: The medical records of children with ONH who had sVEP testing and documented recognition visual acuity at the University of Wisconsin from 2005 to 2013 were reviewed retrospectively. Optic nerve size, amblyopia treatment, and neurologic diagnoses were collected. RESULTS: A total of 57 patients were included: 41 (71%) with bilateral ONH and 27 (47%) with neurologic abnormality. Mean age at initial sVEP was 13.3 months (range, 1-32). Mean duration between initial sVEP and final recognition acuity was 5.5 years (range, 3.5-7). Sweep VEP was associated with ONH severity (P < 0.05). Sweep VEP, and the combination of ONH severity and neurologic status, were significant predictors (P < 0.05) of logMAR optotype acuity, together accounting for 54%-61% of the variance in final recognition acuity. CONCLUSIONS: Sweep VEP in preverbal children with ONH depends on ONH severity and correlates with final recognition visual acuity. Children with milder degrees of ONH without neurologic abnormalities had better final vision, and patients with severe ONH and neurologic diagnoses had worse vision outcomes.

Precursors and Development of Geographic Atrophy with Autofluorescence Imaging: Age-Related Eye Disease Study 2 Report Number 18.

PURPOSE: To describe the sequence of events leading to development of geographic atrophy (GA) in age-related macular degeneration with fundus autofluorescence (FAF) imaging. DESIGN: Post hoc analysis of FAF images from the Age-Related Eye Disease Study 2. PARTICIPANTS: Fundus autofluorescence images of 120 eyes (109 patients) with incident GA and at least 2 years of preceding FAF images. METHODS: Images of incident GA were stacked and aligned over FAF images of preceding annual visits. The regions of retina where incident GA developed were assessed on prior years' FAF images. These regions, defined as precursor lesions, were classified into minimal change autofluorescence, predominant hypoautofluorescence (decreased autofluorescence), predominant hyperautofluorescence (increased autofluorescence), and mixed autofluorescence. The natural progression in precursor lesions leading to GA formation and their associations with incident GA size and GA enlargement rate were evaluated. MAIN OUTCOME MEASURES: Incident GA area and enlargement rate and precursor pattern frequency. RESULTS: Incident GA had a mean area of 1.00 mm2 (range, 0.15-8.22 mm2) and an enlargement rate of 0.97 mm2/year (standard deviation, 1.66 mm2/year). Predominant hypoautofluorescence was the most common precursor lesion, increasing from 42% to 81% over 3 years before onset of GA. Almost 30% of eyes showed minimal change autofluorescence 3 years before GA. Among the other precursors, 70% progressed to predominant hypoautofluorescence before GA developed. The type of precursor lesions was not associated with incident GA area. Geographic atrophy evolving from minimal change autofluorescence precursor lesions was associated with faster GA enlargement rates compared with other precursor lesion classes. CONCLUSIONS: Using image registration, we identified changes in autofluorescence images before the onset of GA. Decreased autofluorescence was the most common change, although minimal changes also were seen in one third of the images. Incident GA that arises from predominantly normal autofluorescence is associated with faster enlargement rates compared with GA arising from abnormal autofluorescence. Faster GA enlargement rates also were associated with incident GA size, area of surround abnormal autofluorescence, and presence of reticular pseudodrusen.

Abnormal Electroretinogram after Kir7.1 Channel Suppression Suggests Role in Retinal Electrophysiology.

The KCNJ13 gene encodes the inwardly rectifying potassium channel, Kir7.1. Mutations in this gene cause childhood blindness, in which the a- and b-wave responses of electroretinogram (ERG) are abolished. The ERG a-wave is the light-induced hyperpolarization of retinal photoreceptors, and the b-wave is the depolarization of ON-bipolar cells. The Kir7.1 channel is localized to the apical aspects of retinal pigment epithelium (RPE) cells and contributes to a delayed c-wave response. We sought to understand why a defect in an RPE ion-channel result in abnormal electrophysiology at the level of the retinal neurons. We have established the expression of Kir7.1 channels in the mouse RPE. ERGs recorded after mice Kir7.1 suppression by shRNA, or by blocking with VU590, showed reduced a-, b- and c-wave amplitudes. In contrast, the Kir7.1 blocker had no effect on the ex-vivo isolated mouse retina ERG where the RPE is not attached to the isolated retina preparation. Finally, we confirmed the specificity of VU590 action by inhibition of native mouse RPE Kir7.1 current in patch-clamp experiment. We propose that mutant RPE Kir7.1 channels contribute directly to the abnormal ERG associated with blindness via alterations in sub-retinal space K+ homeostasis in the vicinity of the photoreceptor outer segment.