Anatomy and evaluation of the optic nerve head / Anatomia e avaliação da cabeça do nervo óptico

ABSTRACT Evaluation of the optic disc is important for the correct diagnosis and follow-up of optic neuropathies, especially glaucoma. The characteristics of the optic disc depend on various factors, including demographic and population aspects, and analysis of these characteristics may vary according to the methods used. The size and format of the neural rim along with the nerve fiber layer are important to the clinician's judgment regarding the susceptibility of the subject to develop glaucoma. In this study, we reviewed the literature to summarize the main methods and its characteristics in the evaluation of the optic nerve head.

RESUMO A avaliação do disco óptico é de suma importância para o diagnostico correto e acompanhamento de neuropatias ópticas, especialmente o glaucoma. Características do disco óptico dependem de uma grande variedade de fatores, incluindo aspectos demográficos e populacionais, e também podem variar de acordo com os métodos usados. Tamanho e formato da rima neurorretiniana junto com a camada de fibras nervosas são importantes ao julgamento clinico a respeito da susceptibilidade do paciente desenvolver glaucoma. Nesse estudo, nós revisamos a literatura para resumir os principais métodos e suas características para a avaliação da cabeça do nervo óptico.

Anatomy and evaluation of the optic nerve head.

Evaluation of the optic disc is important for the correct diagnosis and follow-up of optic neuropathies, especially glaucoma. The characteristics of the optic disc depend on various factors, including demographic and population aspects, and analysis of these characteristics may vary according to the methods used. The size and format of the neural rim along with the nerve fiber layer are important to the clinician's judgment regarding the susceptibility of the subject to develop glaucoma. In this study, we reviewed the literature to summarize the main methods and its characteristics in the evaluation of the optic nerve head.

Elucidation of the role of the lamina cribrosa in glaucoma using optical coherence tomography.

Glaucoma is a chronic and progressive optic neuropathy characterized by the death of retinal ganglion cells and corresponding visual field loss. Despite the growing number of studies on the subject, the pathogenesis of the disease remains unclear. Notwithstanding, several studies have shown that the lamina cribrosa (LC) is considered an anatomic site of glaucomatous optic nerve injury, thus having a key role in the pathophysiology of glaucoma development and progression. Different morphological alterations of the LC have been described in vivo in glaucomatous eyes after the evolution of optical coherence tomography (OCT) devices. The most relevant findings were the reduction of laminar thickness, the presence of localized defects, and the posterior LC displacement. These new laminar parameters documented through OCT are not only promising as possible additional tools for glaucoma diagnosis and monitoring, but also as predictors of disease progression. In spite of the advance of technology, however, proper evaluation of the LC is not yet viable in all eyes. We describe OCT-identified LC changes related to the development and progression of glaucoma and provide future directions based on a critical data analysis, focusing on its clinical relevance and applicability.

Magnetic Resonance Imaging for Glaucoma Evaluation.

The damage caused by glaucoma has been extensively evaluated at the level of the retina and optic nerve head. Many advances have been shown in this field in the last decades. Recent studies have also proved degenerative changes in the brain involving the intracranial optic nerve, lateral geniculate nucleus, and visual cortex. Moreover, these brain abnormalities are also correlated with clinical, optic nerve head, and visual field findings. In this review, we critically evaluate the existing literature studying the use of magnetic resonance imaging in glaucoma, and we discuss issues related to how magnetic resonance imaging results should be incorporated into our clinical practice.

Relationship Between Optic Nerve Head Drusen Volume and Structural and Functional Optic Nerve Damage.

PURPOSE: The purpose of this study is to assess the relationships between optic nerve head drusen (ONHD) volume, retinal nerve fiber layer (RNFL) thickness and visual field (VF) loss. METHODS: Patients with ONHD and no other ocular or systemic conditions that can affect RNFL or VF were enrolled. Serial enhanced depth imaging (EDI) optical coherence tomography (OCT) B-scans of the optic nerve head (interval between scans, ~30 µm) were obtained from each participant. ONHD volume was calculated for each eye by delineating the ONHD masses in each OCT B-scan using 3-dimensional reconstruction software. RESULTS: A total of 47 eyes (28 patients) with ONHD were included (mean age, 57±16 y). ONHD volume varied considerably [0.265±0.227 (range, 0.005 to 0.855)] mm. Linear and quadratic regression analyses demonstrated that ONHD volume is significantly associated with both global average RNFL thickness (linear R=0.531, quadratic R=0.557; P<0.001) and VF mean deviation (linear R=0.519, quadratic R=0.522; P<0.001). ONHD were most prevalent in the nasal quadrant (46 eyes, 98%), followed by superior, inferior and temporal quadrants [35 (74%), 30 (64%), and 16 (34%) eyes respectively]. The proportion of eyes with OCT RNFL defects (81%; 38/47 eyes) was significantly greater than that with VF defects (60%; 28/47 eyes) (P<0.001). RNFL defects were detected in 10 of the 19 eyes with no VF defects. RNFL defects were detected in all 28 eyes with VF defects. CONCLUSIONS: ONHD volume generally correlates with structural and functional optic nerve damage.

In vivo analysis of glaucoma-related features within the optic nerve head using enhanced depth imaging optical coherence tomography.

Structural differences between optic nerve head (ONH) parameters in glaucomatous and non-glaucomatous eyes has been documented, however the association between such parameters in patients with different disease stages is yet to be elucidated. We investigated the relationship between different laminar and prelaminar ONH structures using enhanced depth imaging spectral-domain optical coherence tomography (EDI OCT) in a population with and without glaucoma. In this observational case-control study, we prospectively enrolled healthy individuals and glaucomatous patients with different disease stages. All participants underwent EDI OCT imaging (Heidelberg Engineering). Following ONH parameters were measured on serial vertical B-scans by two examiners masked to patient's clinical data: lamina cribrosa (LC) and prelaminar neural tissue (PLNT) thicknesses, Bruch's membrane opening (BMO) and cup depth. Associations between cup depth, and laminar and prelaminar parameters were evaluated controlling for possible confounding factors such as axial length and disc size. Sixty-four eyes of 64 patients were included (30 with glaucoma and 34 controls). Eyes with glaucoma had significantly lower mean LC and PLNT thickness, and greater mean cup depth than controls (p<0.01). There was a significant negative association between PLNT thickness and cup depth in glaucomatous eyes (R2 = 0.158, p = 0.029). In addition, LC thickness correlated significantly with cup depth (R2 = 0.135, p = 0.045). Eyes with thinner LCs presented deeper cups. Overall, cup depth and BMO had the best and LC thickness had the worst intraobserver and interobserver reproducibility grading. In conclusion, significant associations were seen between cup depth, LC and PLNT thickness. Eyes with deeper cups not only had less neural tissue, but also thinner LCs, independent of disc size and axial length. Best reproducibility was found for prelaminar parameters compared to deeper ONH structures.

Characteristics and variations of in vivo Schlemm's canal and collector channel microstructures in enhanced-depth imaging optical coherence tomography.

BACKGROUND/AIMS: To characterise in vivo Schlemm's canal (SC) and collector channels (CC) microstructures using enhanced-depth imaging (EDI) optical coherence tomography (OCT). METHODS: Serial horizontal EDI OCT B-scans (81 scans, 15×5° rectangle) were prospectively obtained in the nasal and temporal limbus. SC cross-sectional area (CSA) was measured by delineating its lumen in each B-scan. CCs connected to SC were counted. SC CSA and the number of CCs were compared between the nasal and temporal areas. RESULTS: Eleven eyes (11 normal subjects) were included (mean age, 28±5 years). SC and CCs were clearly demarcated in EDI OCT B-scans with excellent repeatability and reproducibility (intraclass correlation coefficients, 0.830-0.886 and 0.793, respectively; all p<0.001). SC CSA varied considerably among subjects, ranging from 1664 to 6007 µm2 (average, 3514±1235 µm2), and among different regions of the same eye with coefficient of variation in each eye ranging from 23% to 46% (average, 32±7%). The number of CCs in the analysed area also varied considerably among subjects, ranging from 5 to 11 (average, 8.73±1.85). The mean SC CSA (3839±1402 µm2 vs 3189±1209 µm2; p=0.033) and number of CCs (5.5±1.4 vs 3.3±1.1; p=0.001) were significantly greater nasally than temporally. The mean SC CSA was significantly correlated with the number of CCs (r=0.635, p=0.036). CONCLUSIONS: High-quality images of the aqueous outflow pathway can be obtained with a clinical device, avoiding postacquisition processing. In vivo SC and CC microstructures vary considerably among individuals and regions. SC tends to be larger in regions with more CCs.

Lamina cribrosa depth in different stages of glaucoma.

PURPOSE: To compare lamina cribrosa (LC) depth between normal eyes and eyes with different stages of treated glaucoma. METHODS: Serial enhanced depth imaging (EDI) optical coherence tomography (OCT) B-scans of the optic nerve head were obtained. To generate the mean LC depth for each eye, LC depths were measured in 11 equally spaced horizontal B-scans and averaged. The mean LC depth was compared among normal, preperimetric, mild-to-moderate, and severe glaucoma groups. Among patients with visual field (VF) loss, correlation analysis was performed (1) between mean LC depth and VF mean deviation (MD), and (2) between mean LC depth and retinal nerve fiber layer (RNFL) thickness. RESULTS: Eighty-six normal eyes (age, 56 ± 14 years), 47 preperimetric glaucoma eyes (age, 60 ± 16 years), 55 mild-to-moderate glaucoma eyes (age, 59 ± 16 years; VF MD, -6.0 ± 3.2 dB), and 60 severe glaucoma eyes (age, 59 ± 17 years; VF MD, -19.7 ± 6.1 dB) were included. Mean LC depth was significantly greater in preperimetric glaucoma than in normal eyes (390 vs. 344 µm, P = 0.004) and in mild-to-moderate than in preperimetric glaucoma eyes (448 vs. 390 µm, P = 0.001). However, no significant difference was observed between mild-to-moderate and severe glaucoma eyes (448 vs. 437 µm, P = 0.52). No correlation was observed between LC depth and VF MD (P = 0.56) or RNFL thickness (P = 0.90) in glaucomatous eyes with VF loss. CONCLUSIONS: In treated glaucoma, posterior LC displacement occurs mostly in the preperimetric and mild-to-moderate glaucoma stages. This warrants further investigation of LC depth as a parameter to monitor glaucoma progression in the early stages.

Analysis of neuroretinal rim distribution and vascular pattern in eyes with presumed large physiological cupping: a comparative study.

BACKGROUND: To investigate possible differences in neuroretinal rim distribution, vascular pattern, and peripapillary region appearance between eyes with presumed large physiological optic disc cupping (pLPC) and eyes with minimal optic disc excavation. METHODS: We prospectively enrolled consecutive subjects with pLPC and individuals with minimal excavation (optic disc excavation within normal limits; control group). All eyes had normal visual fields and untreated intraocular pressure (IOP) <21 mmHg. Eyes with pLPC required vertical cup-to-disc ratio (VCDR) ≥ 0.6 and ≥ 30 months of follow-up with no evidence of glaucomatous neuropathy. For controls, VCDR was limited to ≤ 0.5. We compared ocular signs and characteristics related to the neuroretinal rim distribution, vascular pattern, peripapillary region appearance and disc size between groups. Whenever both eyes were eligible, one was randomly selected for analysis. RESULTS: A total of 74 patients (mean age, 45.6 ± 14.9 years) with pLPC and 45 controls (mean age, 44.8 ± 11.6 years) were enrolled (p = 0.76). Median disc size and VCDR was significantly larger in eyes with pLPC compared to controls (p < 0.01). The proportion of eyes with violation of the ISNT rule, laminar dot sign, nasal shifting of the central vessels, nasal excavation and baring of circumlinear vessel was significantly greater in the eyes with pLPC compared to controls (p < 0.01). There were no significant differences regarding the proportions of eyes with peripapillary atrophy between groups (p < 0.09). Finally, disc size was significantly associated with VCDR (r(2) = 0.47, p < 0.01), with an increase of 0.21 in VCDR for each 1 mm(2) in disc area. CONCLUSION: Compared to normal controls, eyes with pLPC may present a higher proportion of optic nerve head findings frequently observed in glaucomatous eyes. This seems to be explained in part by the larger discs found in these eyes. We believe care should be taken while classifying them as glaucomatous or not based solely on these characteristics.

A new index to monitor central visual field progression in glaucoma.

PURPOSE: The visual field index (VFI) summarizes global visual field (VF) data and was developed to monitor glaucoma progression using 24-2 and 30-2 strategies. We applied similar principles and statistical procedures to develop a new parameter, the central field index (CFI), to monitor 10-2 VF progression. DESIGN: Retrospective cohort. PARTICIPANTS: Glaucoma patients with paracentral defects seen on 24-2 perimetry and followed up with at least 5 10-2 VF tests. METHODS: The CFI was developed by calculating age-corrected defect depth at test points obtained during 10-2 examinations. The sensitivities at these points were scored as percentages similar to the method described for the VFI: 100-[(|total deviation|/age-corrected normal threshold) × 100]. A weighting procedure was applied based on published estimates of the occipital cortical spatial magnification. For validation, we performed mixed linear model testing for the association between CFI rates of change (%/year) and known risk factors for glaucoma progression in a population with established glaucoma and at least 5 10-2 VF tests. To determine whether the CFI was affected by cataract, as is known to occur with mean deviation (MD), we conducted a pilot evaluation comparing rates of CFI change in 3 groups: (1) eyes with cataract, (2) pseudophakic eyes, and (3) eyes in which cataract surgery was performed in the middle of the series. MAIN OUTCOME MEASURES: Rates of CFI and MD change. RESULTS: Central field index values were calculated for 176 eyes of 142 patients. The mean rate of CFI change of the entire sample was -1.10%/year (95% confidence interval, -1.03 to -1.16%/year). Elevated intraocular pressure (P<0.001) was associated significantly with faster CFI change, whereas lens status did not influence CFI rates of change (P>0.100) CONCLUSIONS: We developed and validated a new index to monitor central field progression that is minimally affected by the presence or removal of cataract and that correlates significantly with an important risk factor for glaucoma progression. This new index may become useful for glaucoma management, especially when combined with conventional static perimetry strategies.

Risk factors for optic disc hemorrhage in the low-pressure glaucoma treatment study.

PURPOSE: To investigate risk factors for disc hemorrhage detection in the Low-Pressure Glaucoma Treatment Study. DESIGN: Cohort of a randomized, double-masked, multicenter clinical trial. METHODS: Low-Pressure Glaucoma Treatment Study patients with at least 16 months of follow-up were included. Exclusion criteria included untreated intraocular pressure (IOP) of more than 21 mm Hg, visual field mean deviation worse than -16 dB, or contraindications to study medications. Patients were randomized to topical treatment with timolol 0.5% or brimonidine 0.2%. Stereophotographs were reviewed independently by 2 masked graders searching for disc hemorrhages. The main outcomes investigated were the detection of disc hemorrhage at any time during follow-up and their recurrence. Ocular and systemic risk factors for disc hemorrhage detection were analyzed using the Cox proportional hazards model and were tested further for independence in a multivariate model. RESULTS: Two hundred fifty-three eyes of 127 subjects (mean age, 64.7 ± 10.9 years; women, 58%; European ancestry, 71%) followed up for an average ± standard deviation of 40.6 ± 12 months were included. In the multivariate analysis, history of migraine (hazard ratio [HR], 5.737; P = .012), narrower neuroretinal rim width at baseline (HR, 2.91; P = .048), use of systemic ß-blockers (HR, 5.585; P = .036), low mean systolic blood pressure (HR, 1.06; P = .02), and low mean arterial ocular perfusion pressure during follow-up (HR, 1.172; P = .007) were significant and independent risk factors for disc hemorrhage detection. Treatment randomization was not associated with either the occurrence or recurrence of disc hemorrhages. CONCLUSIONS: In this cohort of Low-Pressure Glaucoma Treatment Study patients, migraine, baseline narrower neuroretinal rim width, low systolic blood pressure and mean arterial ocular perfusion pressure, and use of systemic ß-blockers were risk factors for disc hemorrhage detection. Randomization assignment did not influence the frequency of disc hemorrhage detection.

Defining 10-2 visual field progression criteria: exploratory and confirmatory factor analysis using pointwise linear regression.

PURPOSE: To test different visual field progression criteria using trend analysis in a glaucoma population followed with long sequences of 10-2 tests as a first attempt to understand and document rates of progression in the central field. DESIGN: Retrospective cohort study. PARTICIPANTS: We included 146 eyes of 146 patients with established glaucoma. METHODS: Pointwise linear regression analysis using the methods of ordinary least squares was performed on the 68 test locations of the 10-2 visual field sequences. Threshold sensitivities at each test location were plotted as the dependent variable against follow-up time as the independent variable. Statistically significant progression or improvement of a visual field test point was defined if its regression slope measured ≤-1.0 dB/year or ≥+1.0 dB/year, respectively, at P<0.01. We explored sets of criteria to define visual field progression, generating a hypothetical sensitivity (progression), specificity (improvement), and progression-to-improvement ratio (PIR) for each criterion. The criterion with the highest PIR was deemed the one with best performance. Latent class analysis (LCA) was used to determine visual field sectors with highest inter-correlation. MAIN OUTCOME MEASURES: The performance of different visual field progression criteria to detect fast rates of mean deviation (MD) change. RESULTS: Median baseline 10-2 MD value was -12.0 dB (interquartile range [IQR], -6.7 to -17.8 dB), and the median rate of 10-2 MD change over time was -0.38 dB/year (IQR, -0.07 to -0.77 dB/year). The highest PIR was obtained with the progression criterion requiring at least 3 test points located in the same LCA-derived 10-2 visual field sector progressing faster than -1.0 dB/year at P<0.01. This criterion was further validated for content and convergence. CONCLUSIONS: This is the first study to investigate progression criteria for 10-2 visual fields using rates of change and to test their performance and validity. These findings may be useful to improve the monitoring of patients with glaucoma at different levels of functional loss and to develop new perimetric algorithms that scrutinize specific visual field locations for a more accurate detection of progression.

Posterior displacement of the lamina cribrosa in glaucoma: in vivo interindividual and intereye comparisons.

PURPOSE: We assessed in vivo lamina cribrosa (LC) position within the optic nerve head in glaucoma. METHODS: For interindividual comparison, glaucoma patients at various stages and normal subjects were recruited. For intraindividual, intereye comparison, glaucoma patients with visual field (VF) defects in only one eye were recruited separately. Serial horizontal and vertical enhanced depth imaging optical coherence tomography (EDI OCT) B-scans of the optic nerve head were obtained prospectively from each participant. Mean and maximum anterior LC depths were measured in 11 equally spaced horizontal B-scans, excluding the LC insertion area under the Bruch's membrane and scleral rim. RESULTS: Totals of 47 glaucomatous eyes (47 patients; VF mean deviation, -12.7±8.2 dB) and 57 normal eyes (57 subjects) were enrolled for the interindividual comparison. Mean and maximum LC depths were significantly greater in the glaucomatous than in the normal eyes in all 11 scans (all P<0.03). There were 54 glaucoma patients with VF defects in only one eye (VF mean deviation, -15.6±8.8 dB) included in the intereye comparison. Mean and maximum LC depths were significantly greater in the eyes with VF defects than in the fellow eyes with no VF defects in all 11 scans (all P<0.01). CONCLUSIONS: The central and midperipheral LC is located more posteriorly in glaucomatous than in normal eyes, as well as in eyes with VF defects compared to fellow eyes with no VF defects. These results support the concept of posterior LC displacement in glaucoma and provide the basis for future in vivo human studies.

Parafoveal scotoma progression in glaucoma: humphrey 10-2 versus 24-2 visual field analysis.

OBJECTIVE: To compare the performance of 10-2 versus 24-2 visual fields (VFs) in detecting progression of initial parafoveal scotoma (IPFS) in glaucomatous eyes. DESIGN: Retrospective, observational study. PARTICIPANTS: Glaucoma patients with the following criteria: (1) an IPFS (≥ 3 adjacent points with P<0.05 within the central 10° degrees of fixation, 1 point or more with P<0.01 lying at the innermost paracentral points, and no scotoma outside the central 10°) in either hemifield based on 2 reliable Humphrey 24-2 Swedish interactive threshold algorithm standard VFs, and (2) 5 or more 10-2 and 24-2 VFs. METHODS: Based on threshold map sensitivities, VF progression, defined as having 1 or more significantly progressing point(s) with a slope of sensitivity of less than -1.0 dB/year at P<0.01, was evaluated using pointwise linear regression. MAIN OUTCOME MEASURES: The number of progressing eyes in 10-2 and 24-2 VF analyses. RESULTS: Fifty eyes (50 patients) were included (mean age ± standard deviation, 62 ± 9 years). Mean follow-up period (5.7 vs. 5.6 years) and number of VFs (7.6 vs. 7.8) were similar between 10-2 and 24-2 analyses (all P>0.3). Significantly more progressing eyes were detected in 10-2 than in 24-2 analyses (24 vs. 11 eyes; P = 0.007). This difference became greater within the central 10° (24 vs. 4 eyes; P<0.001). Four of the 11 progressing eyes in 24-2 analysis were missed in 10-2 analysis, whereas 17 of the 24 progressing eyes in 10-2 analysis were missed in 24-2 analysis. The 4 progressing eyes missed in 10-2 analysis had progressing point(s) only outside the central 10° in 24-2 analysis. The other 3 eyes with progressing point(s) only outside the central 10° in 24-2 analysis were detected as progressing in 10-2 analysis. Similar results were obtained when more stringent criteria (at least 2 significantly progressing points within the same hemifield) were used for VF progression. CONCLUSIONS: The 10-2 VF detects more progressing eyes than the 24-2 VF in glaucoma patients with IPFS, suggesting that closer surveillance of the central VF using testing algorithms with closely spaced grids is warranted in eyes with parafoveal scotomas. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Infectious keratitis secondary to Histoplasma capsulatum: the first case reports in humans

The authors report an unusual case of fungal keratitis caused by Histoplasma capsulatum in a male immunocompetent patient. PCR confirmed the presence of the fungus DNA in the material studied. To our knowledge this is the first reported case in humans described all over the world.

Infectious keratitis secondary to Histoplasma capsulatum: the first case reports in humans.

The authors report an unusual case of fungal keratitis caused by Histoplasma capsulatum in a male immunocompetent patient. PCR confirmed the presence of the fungus DNA in the material studied. To our knowledge this is the first reported case in humans described all over the world.