Comparative Assessment of Retinal Blood Flow Velocity Changes Following Brimonidine and Brinzolamide Administration Using Retinal Function Imaging.

PURPOSE: Impaired ocular blood flow has been associated with the etiopathogenesis of glaucoma. Topical brimonidine lowers intraocular pressure, a major glaucoma risk factor. However, brimonidine's influence on retinal blood flow remains to be fully elucidated. Our aim was to compare the effect of topical brimonidine and brinzolamide administration on retinal blood flow velocity in second and third order vessels in healthy adults using the retinal function imager. METHODS: In 10 healthy probands between 23 and 32 years of age, one eye was randomly selected to receive 2 treatment rounds with 3 single doses of brimonidine 2 mg/mL and brinzolamide 10 mg/mL at 12-hour intervals each. The fellow eyes served as intra-individual controls. Immediately before the first drop and 2 hours after the last drop of each treatment round, all subjects were examined, including Goldmann tonometry, Pascal tonometry, assessment of retinal blood flow velocity using the retinal function imager, as well as blood pressure and pulse measurements. RESULTS: Intraocular pressure decreased significantly in treated eyes while remaining stable in control eyes, indicating reliable application of brimonidine and brinzolamide drops. In contrast, retinal blood flow velocities did not demonstrate any significant differences between groups after both treatment rounds. CONCLUSIONS: Neither brimonidine nor brinzolamide appear to alter retinal blood flow velocity in a clinically relevant manner. The slight velocity changes detected in our study are likely physiologic fluctuations. Our findings do not support the rationale of a detrimental effect of topical brimonidine on ocular blood flow and hence brimonidine may be further administered for lowering intraocular pressure with the appropriate caution. However, our study is strongly limited by the small sample size and, thus, further research with larger cohorts of healthy volunteers and patients with glaucoma is needed to confirm the results. TRANSLATIONAL RELEVANCE: The study provides information about the effect of the topically administered antiglaucoma medications brimonidine and brinzolamide on the ocular blood flow and its regulation. The findings indicate that beside the lowering of IOP there is no evidence for an additional effect on the development of glaucoma.

Analysis of Microvasculature in Nonhuman Primate Macula With Acute Elevated Intraocular Pressure Using Optical Coherence Tomography Angiography.

Purpose: To investigate responses of macular capillary vessel area density (VAD) of superficial and deep retinal vascular plexuses to elevations in intraocular pressure (IOP) in cynomolgus macaque monkeys using optical coherence tomography angiography (OCTA). Methods: In five general anesthetized male cynomolgus monkeys, the IOP was increased incrementally by 10 mmHg from baseline (10 mmHg) to 70 mmHg and then decreased back to 10 mmHg (recovery state). Structural OCT (30° × 30°) and OCTA (20° × 15°) centered on the macula were obtained at each IOP and 3, 15, and 30 minutes after recovery. En face images of the superficial vascular complex (SVC) and deep vascular complex (DVC) were extracted, and VAD (%) compared with that at baseline was calculated. Results: The VADs in the SVC and DVC at baseline and at 30 mmHg IOP were 34.96%, 34.15%, 35.38%, and 30.12%, respectively. The VAD plateaued until 30 mmHg; however, the VAD was affected more in the DVC than in the SVC (P = 0.008) at 30 mmHg. It showed a significant reduction at 40 mmHg (16.52% SVC, P = 0.006; 18.59% DVC, P = 0.012). In the recovery state, the SVC showed full retention of baseline VAD, but the DVC maintained VAD approximately 70% of that at baseline. Structural OCT showed hyperreflectivity in the nuclear layer, retinal swelling, and an undifferentiated ellipsoid zone from 50 mmHg. Conclusions: Despite physiological autoregulation, perifoveal microcirculation was affected at high IOP ≥ 40 mmHg, especially in the DVC, which explains the pathological mechanism of macular vulnerability in ischemic diseases.

Interplay between intraocular and intracranial pressure effects on the optic nerve head in vivo.

Intracranial pressure (ICP) has been proposed to play an important role in the sensitivity to intraocular pressure (IOP) and susceptibility to glaucoma. However, the in vivo effects of simultaneous, controlled, acute variations in ICP and IOP have not been directly measured. We quantified the deformations of the anterior lamina cribrosa (ALC) and scleral canal at Bruch's membrane opening (BMO) under acute elevation of IOP and/or ICP. Four eyes of three adult monkeys were imaged in vivo with OCT under four pressure conditions: IOP and ICP either at baseline or elevated. The BMO and ALC were reconstructed from manual delineations. From these, we determined canal area at the BMO (BMO area), BMO aspect ratio and planarity, and ALC median depth relative to the BMO plane. To better account for the pressure effects on the imaging, we also measured ALC visibility as a percent of the BMO area. Further, ALC depths were analyzed only in regions where the ALC was visible in all pressure conditions. Bootstrap sampling was used to obtain mean estimates and confidence intervals, which were then used to test for significant effects of IOP and ICP, independently and in interaction. Response to pressure manipulation was highly individualized between eyes, with significant changes detected in a majority of the parameters. Significant interactions between ICP and IOP occurred in all measures, except ALC visibility. On average, ICP elevation expanded BMO area by 0.17 mm2 at baseline IOP, and contracted BMO area by 0.02 mm2 at high IOP. ICP elevation decreased ALC depth by 10 µm at baseline IOP, but increased depth by 7 µm at high IOP. ALC visibility decreased as ICP increased, both at baseline (-10%) and high IOP (-17%). IOP elevation expanded BMO area by 0.04 mm2 at baseline ICP, and contracted BMO area by 0.09 mm2 at high ICP. On average, IOP elevation caused the ALC to displace 3.3 µm anteriorly at baseline ICP, and 22 µm posteriorly at high ICP. ALC visibility improved as IOP increased, both at baseline (5%) and high ICP (8%). In summary, changing IOP or ICP significantly deformed both the scleral canal and the lamina of the monkey ONH, regardless of the other pressure level. There were significant interactions between the effects of IOP and those of ICP on LC depth, BMO area, aspect ratio and planarity. On most eyes, elevating both pressures by the same amount did not cancel out the effects. Altogether our results show that ICP affects sensitivity to IOP, and thus that it can potentially also affect susceptibility to glaucoma.

Persistência da vasculatura fetal diagnosticada pela ultrassonografia ­ Relato de caso / Vasculature persistence fetal diagnosed by ultrasound ­ case report

Contexto: A persistência da vasculatura fetal é uma malformação ocular rara em adultos, habitualmente unilateral, sendo uma condição não hereditária, com poucas manifestações sistêmicas e neurológicas. Descrição do caso: Homem de 45 anos queixando-se de dor no olho esquerdo, com pressão intraocular de 56 mmHg. A ultrassonografia do olho esquerdo demonstra aumento da ecogenicidade do cristalino inferindo catarata e redução da amplitude da câmara anterior, membrana posterior hiperecogênica no interior da câmara vítrea com intensa vascularização com fluxo arterial ao estudo com Doppler, caracterizando a persistência da vasculatura fetal. O paciente recebeu tratamento por três dias. Com a redução da pressão intraocular após esse período, realizou a cirurgia combinada de facoemulsificação com implante de lio e implante de tubo de Ahmed. Após o procedimento cirúrgico, o paciente não voltou a apresentar a sintomatologia. Discussão: Clinicamente, há duas condições de doença, dependendo da porção atingida do vítreo primário ­ as formas anterior e posterior. A persistência da vasculatura fetal não tratada frequentemente progride para phthisis bulbi ou enucleação devido a uma hemorragia intraocular recorrente e secundária ao glaucoma. Os esforços cirúrgicos têm o intuito de preservar a visão. Conclusão: Relatamos um caso de persistência da vasculatura fetal diagnosticado pela ultrassonografia e tratado cirurgicamente com sucesso devido ao alívio dos sintomas em olho esquerdo sem percepção luminosa.

The Macular Choriocapillaris Flow in Glaucoma and Within-Day Fluctuations: An Optical Coherence Tomography Angiography Study.

Purpose: To assess quantitatively the choriocapillaris (CC) perfusion area in the macular area of healthy eyes, eyes with primary open-angle glaucoma, and eyes with ocular hypertension using optical coherence tomography angiography (OCTA). Methods: A consecutive series of healthy individuals and patients with glaucoma and ocular hypertension were recruited prospectively in this single-center, cross-sectional study based in Milan, Italy. OCTA was performed in the morning and evening, along with a complete ophthalmologic examination. Macular superficial capillary plexus vessel density (SCP-VD) and the thicknesses of the retina and ganglion cell complex (GCC), as well as their fluctuations, were investigated. Results: Thirty-nine eyes from 24 individuals with glaucoma (mean age = 58.79 ± 6 years), 43 eyes from 27 individuals with ocular hypertension (59.19 ± 6 years), and 54 eyes from 35 controls (58.27 ± 6 years) were enrolled. The mean CC perfusion area values were not significantly different among the three groups in the morning or evening (P ≥ 0.47). In contrast, SCP-VD, retinal thickness, and GCC thickness were statistically different among the groups (P ≤ 0.016), except for the foveal SCP-VD (P ≥ 0.19) and the evening foveal thickness (P = 0.57). Diurnal changes in the CC perfusion area, SCP-VD, retinal thickness, and GCC thickness were not statistically significant (P ≥ 0.16). Systemic hypertension, sex, age, axial length, and diurnal changes in intraocular pressure were not significantly associated with morning or evening measurements, or with diurnal fluctuations (P ≥ 0.07). Conclusions: The macular CC flow perfusion area appears unaffected in eyes with primary open-angle glaucoma. No significant diurnal changes were observed in any of the parameters investigated.

Relationship between Three-Dimensional Magnetic Resonance Imaging Eyeball Shape and Optic Nerve Head Morphology.

PURPOSE: To determine if the 3-dimensional (3D) eyeball shape is associated with the positions of the central retinal vascular trunk (CRVT) and the externally oblique border (EOB) in the optic nerve head (ONH). DESIGN: Prospective, cross-sectional study. PARTICIPANTS: Fifty-six subjects (112 eyes) with a diagnosis of glaucoma or glaucoma suspect. METHODS: The eyeball shape on 3D magnetic resonance imaging (MRI) scans was classified according to the dimension of the longest diameter: axial dimension (prolate sphere), group 1; horizontal dimension (horizontally oblate sphere), group 2; and vertical dimension (vertically oblate sphere), group 3. The deviation of the CRVT, as a surrogate of lamina cribrosa (LC) shift, was measured from the center of the Bruch's membrane opening (BMO) demarcated by OCT imaging, with the horizontal midline as 0° and the superior location as a positive value. The angular location of the longest EOB was also measured. MAIN OUTCOME MEASURE: Positions of CRVT and EOB according to the 3D eyeball shape. RESULTS: Among 112 eyes, 54 (48%) had a prolate shape (group 1), 23 (21%) had a horizontally oblate shape (group 2), and 35 (31%) had a vertically oblate shape (group 3). The angular deviation of the CRVT differed among the groups: to the nasal side in group 1, to the temporal side in group 2, and along the vertical meridian in group 3. In cases of asymmetric eyeball shape, the CRVT was deviated toward the undergrown side from the overgrown side, regardless of grouping. The angular location of the longest EOB was in the direction opposite to the CRVT position (P < 0.001). A generalized estimating equation analysis revealed that the temporal location of the CRVT was associated with older age (P = 0.001), nasal location of the longest EOB (P < 0.001), and oblate shape of the eyeball (P < 0.001, group 2; P = 0.007, group 3). CONCLUSIONS: The position of the CRVT and EOB were associated with the 3D eyeball shape. Considering that infant ONH morphology is highly uniform, various modes of eyeball expansion during growth can result in diverse directionalities of offset between the LC and the BMO in adults.

Functional and morphological alterations in a glaucoma model of acute ocular hypertension.

To study short and long-term effects of acute ocular hypertension (AOHT) on inner and outer retinal layers, in adult Sprague-Dawley rats AOHT (87mmHg) was induced for 90min and the retinas were examined longitudinally in vivo with electroretinogram (ERG) recordings and optical coherent tomography (OCT) from 1 to 90 days (d). Ex vivo, the retinas were analyzed for rod (RBC) and cone (CBC) bipolar cells, with antibodies against protein kinase Cα and recoverin, respectively in cross sections, and for cones, horizontal (HZ) and ganglion (RGC) cells with antibodies against arrestin, calbindin and Brn3a, respectively in wholemounts. The inner retina thinned progressively up to 7d with no further changes, while the external retina had a normal thickness until 30d, with a 20% thinning between 30 and 90d. Functionally, the a-wave showed an initial reduction by 24h and a further reduction from 30 to 90d. All other main ERG waves were significantly reduced by 1d without significant recovery by 90d. Radial sections showed a normal population of RBCs but their terminals were reduced. The CBCs showed a progressive decrease with a loss of 56% by 30d. In wholemount retinas, RGCs diminished to 40% by 3d and to 16% by 30d without further loss. Cones diminished to 58% and 35% by 3 and 7d, respectively and further decreased between 30 and 90d. HZs showed normal values throughout the study. In conclusion, AOHT affects both the inner and outer retina, with a more pronounced degeneration of the cone than the rod pathway.

The Relationship Between Corneal Hysteresis and Retinal Ganglion Cells - A Step Forward in Early Glaucoma Diagnosis.

BACKGROUND Glaucoma is a major cause of irreversible visual field (VF) loss across the world. Many studies have assessed the accuracy of glaucoma diagnostic tests for a more precise diagnosis to quickly identify patients with higher risk of progression. MATERIAL AND METHODS We conducted a study that included 214 eyes divided into 3 groups: 79 eyes from patients diagnosed with primary open-angle glaucoma (POAG), 68 eyes from patients diagnosed with ocular hypertension (OH), and 67 eyes from normal individuals (normal eyes, NE). All patients included in the study received a complete checkup. RESULTS In POAG patients, means of central corneal thickness (CCT), corneal hysteresis (CH), corneal resistance factor (CRF), mean defect (MD), visual field index (VFI), peripapillary retinal nerve fiber layer (pRNFL), and ganglion cell complex (GCC) are lower than in OH patients, and in NE are higher than in both groups. Also, we found a statistically significant direct correlation between CH and GCC thickness. Further statistical analysis revealed that both pRNFL thickness and GCC thickness are significantly influenced by CH value in a precise manner. CONCLUSIONS The first cell type affected in glaucoma is the retinal ganglion cell. We found a positive correlation between GCC thickness and CH, suggesting that CH might be a parameter to consider in the evaluation of all glaucoma patients from their first examination. Moreover, both pRNFL thickness and GCC thickness are influenced by CH, suggesting the utility of monitoring the value of CH at every checkup to detect its decrease in glaucoma patients.

A Topographic Comparison of OCT Minimum Rim Width (BMO-MRW) and Circumpapillary Retinal Nerve Fiber Layer (cRNFL) Thickness Measures in Eyes With or Suspected Glaucoma.

PRéCIS:: Bruch's membrane opening-minimum rim width (BMO-MRW) and circumpapillary retinal nerve fiber layer (cRNFL) thickness measures may be improved by comparing probability levels and accounting for blood vessel locations. PURPOSE: To understand the differences between 2 optical coherence tomography measures of glaucomatous damage: the BMO-MRW and cRNFL thickness. MATERIALS AND METHODS: Optical coherence tomography circle scans were obtained for an early glaucoma group (EG) of 88 eyes (88 patients) with 24-2 mean deviation better than -6.0 dB, and a broader group (BG) of 188 eyes (110 patients) with 24-2 mean deviation from -0.15 to -27.0 dB. On the basis of a commercial report, the cRNFL and BMO-MRW of each hemidisc was classified as abnormal if either of the 2 superior (inferior) sectors, temporal superior and nasal superior (temporal inferior and nasal inferior), was yellow or red (P<5%); and as normal if both were green (P≥5%). In addition, a post hoc analysis identified the reasons for disagreements on the basis of the presence (or absence) of glaucomatous damage at a hemidisc level (consensus of 4 experts). RESULTS: The BMO-MRW and cRNFL measures agreed in 81.9% (broader group) and 73.9% (EG) of the hemidiscs. In both groups, an abnormal-BMO-MRW/normal-cRNFL disagreement was as common as a normal-BMO-MRW/abnormal-cRNFL. Of the 46 EG hemidisc disagreements, the number of "mistakes" for BMO-MRW (28) was nonsignificantly higher than for cRNFL (18) (P=0.15). Primary causes for disagreement were as follows: borderline significance level, a local defect, and aberrant blood vessel location. CONCLUSIONS: Although BMO-MRW and cRNFL measures agreed in the majority of hemidiscs, they still disagreed in over 25% of the EG hemidiscs. These measures may be improved by comparing actual probability levels and accounting for blood vessel locations. However, both can miss information available on retinal ganglion cell/retinal nerve fiber layer probability maps.

Clinical Utility of Triplicate En Face Image Averaging for Optical Coherence Tomography Angiography in Glaucoma and Glaucoma Suspects.

PRéCIS:: Averaging triplicate en face angiograms of the radial peripapillary capillary (RPC) plexus with optical coherence tomography angiography (OCTA) improves vessel visualization, reduces vessel density parameters, and increases the diagnostic accuracy for glaucoma of one such parameter. PURPOSE: The purpose of this study was to test the hypothesis that triplicate averaging of the RPC layer improves visualization and diagnostic accuracy of OCTA for glaucoma. MATERIALS AND METHODS: This is a cross-sectional study involving 63 primary open-angle glaucoma patients and 70 age-matched glaucoma suspects. Triplicate 6×6 mm OCTA scans of the optic nerve head were acquired, and the RPC layer was extracted. RPC en face images were registered and averaged. Parameters of global entropy, global standard deviation, local texture correlation, local homogeneity, signal-to-noise ratio, and intercapillary distance were used to measure the change in visualization with averaging. Vessel area density (VAD), vessel skeleton density (VSD), and flux parameters were calculated in a 2.8 mm annulus excluding the optic disc. The diagnostic accuracy of these parameters for glaucoma was assessed by calculating the area under the receiver operating curve (AUC) values. RESULTS: Three-frame averaging resulted in decreased global entropy and global standard deviation (Ps<0.001), and increased local texture correlation, local homogeneity, signal-to-noise ratio, and intercapillary distance (Ps<0.001). Averaged images also had reduced VAD, VSD, and flux (Ps<0.001). AUC was significantly increased for VSD after image averaging (P=0.018), while no significant change in AUC was observed for VAD (P=0.229) or flux (P=0.193). CONCLUSIONS: Triplicate averaging improves visualization of the RPC layer and the diagnostic accuracy of VSD for glaucoma. The impact of image averaging on OCTA diagnostic performance and other potential applications warrants further exploration.

Assessing the Impact of En Face Retinal Nerve Fiber Layer Imaging on Clinical Decision Making for Glaucoma Suspects.

SIGNIFICANCE: Assessing and managing glaucoma are a complicated process in which experience plays a key role in decision making. Although advanced glaucoma is more easily diagnosed, patients with early glaucoma or who present with suspicious findings are more complicated. A need to aid clinicians in the decision-making process exists. PURPOSE: The purpose of this study was to assess the impact of en face ocular coherence tomography images to clinical decision making when added to standard presentations of circumpapillary retinal nerve fiber layer thickness and automated perimetry. METHODS: Thirty participants from two centers presenting either as a glaucoma suspect or for an initial glaucoma evaluation were enrolled. Six masked investigators were given standard presentations of circumpapillary retinal nerve fiber layer thickness and perimetry. They were asked if glaucomatous damage was present as well as a recommended plan of management on 5-point Likert scales. They were then given en face images of the retinal nerve fiber layer in three different presentations coupled with the standard presentation, and the questions were repeated. An intraclass correlation coefficient (ICC) was generated. RESULTS: The masked investigators had moderate agreement from the standard presentation for assessment (ICC = 0.67 [95% confidence interval {CI}, 0.54 to 0.80] and ICC = 0.69 [95% CI, 0.52 to 0.80], respectively), as well as with the addition of the en face images (ICC = 0.69; 95% CI, 0.56 to 0.81). The en face images tended to change decisions in both assessment and plan toward likely to have glaucoma and likely to start treatment. CONCLUSIONS: The addition of en face images to a standard presentation has an impact on clinical decision making. Although en face images seem to influence the decision toward likely to have glaucoma and likely to treat, it is unclear if this leads to a more accurate decision. Further investigations seem warranted to assess sensitivity and specificity of this approach.

A clinical method for estimating the modulus of elasticity of the human cornea in vivo.

BACKGROUND: To develop a method, using current clinical instrumentation, to estimate the Young's modulus of the human cornea in vivo. METHODS: Central corneal curvature (CCC), central corneal thickness(CCT), intraocular pressure (IOP) was measured with the Goldmann tonometer (IOPG) and the Pascal Dynamic Corneal Tonometer(PDCT) in one eye of 100 normal young human subjects (21.07 ± 2.94 years) in vivo. The Orssengo and Pye algorithm was used to calculate the Young's modulus of the corneas of these subjects. RESULTS: The Young's modulus(E) of the corneas of the subjects using the PDCT and IOPG results (Ecalc) was 0.25 ± 0.10MPa, and without the PDCT results (Eiopg) was 0.29 ± 0.06MPa. The difference in these results is due to the difference in tonometry results between the two instruments, as the mean PDCT result for the subjects was 16.89 ± 2.49mmHg and the IOPG result 15.06 ± 2.71mmHg. E was affected by the CCC of the subjects but more particularly by the CCT and IOP measurements. Corneal stiffness results are also presented. CONCLUSION: Two methods have been developed to estimate the Young's modulus of the human cornea in vivo using current clinical instrumentation. One method (Ecalc) is applicable to the general corneal condition, and Eiopg to the normal cornea, and these results can be used to calculate corneal stiffness.

Optical Coherence Tomography Structural Abnormality Detection in Glaucoma Using Topographically Correspondent Rim and Retinal Nerve Fiber Layer Criteria.

PURPOSE: This study evaluated the ability of topographically correspondent (TC) minimum rim width (MRW) and peripapillary retinal nerve fiber layer thickness (pRNFLT) criteria to detect optical coherence tomography (OCT) structural abnormality in glaucoma (GL) and glaucoma suspect (GLS) eyes. DESIGN: Retrospective cross-sectional study. METHODS: A total of 196 GL eyes, 150 GLS eyes, and 303 heathy eyes underwent pRNFL and 24 radial optic nerve head OCT imaging and manual correction of the internal limiting membrane, Bruch's membrane opening (BMO), and outer pRNFL segmentations. MRW and pRNFLT were quantified in 6 Garway-Heath or 12 30-degree (clock-hour) sectors. OCT abnormality for each parameter was defined to be less than the 5th percentile of the healthy eye distribution. OCT abnormality for individual eyes was defined using global, sectoral, and combined parameter criteria that achieved ≥95% specificity in the healthy eyes. TC combination criteria required the sectoral location of MRW and pRNFLT abnormality to be topographically aligned and included comMR (a previously reported TC combination consisting of MRW and pRNFLT parameter: [MRW + pRNFLT × (average MRW healthy eyes/average pRNFLT healthy eyes) MRW]. RESULTS: TC sectoral criteria (1 Garway-Heath MRW + corresponding Garway-Heath RNFLT), (one 30-degree MRW + any 1 corresponding or adjacent 30-degree pRNFLT), 30-degree and Garway-Heath comMR-TI and global comMR were the best performing criteria, demonstrating (96%-99% specificity), 86%-91% sensitivity for GL, 80%-84% sensitivity for early GL (MD ≥ -4.0 dB) and 93%-96% sensitivity for moderate-to-advanced GL (MD < -4.0 dB). CONCLUSIONS: Clinically intuitive TC MRW and pRNFLT combination criteria identified the sectoral location of OCT abnormality in GL eyes with high diagnostic precision.

Phacolytic glaucoma: A nearly forgotten entity.

PURPOSE: To report a case of phacolytic glaucoma with rupture of anterior lens capsule in a case of hypermature cataract. METHODS: Case report and literature review. RESULTS: An 80-year-old woman presented with cloudiness and pain in the left eye for 1 day. The patient had visual acuity limited to perception of light with raised intraocular pressure of 70 mm Hg. Careful slit-lamp evaluation revealed corneal epithelial edema in superior quadrant and a deep and turbid anterior chamber. Ultrasound biomicroscopy confirmed the presence of a deep anterior chamber, a hypermature cataractous nucleus with lax capsular bag, and ruptured anterior lens capsule. The patient underwent extracapsular cataract extraction. Cytological examination of the lenticular fluid revealed the presence of lens protein-laden macrophages. Post-operatively, the patient had best-corrected visual acuity of 6/60 with advanced glaucomatous optic neuropathy. CONCLUSION: Phacolytic glaucoma can present with a cloudy cornea and a turbid anterior chamber mimicking endophthalmitis. Careful examination and ancillary investigations including ultrasound biomicroscopy was helpful in making an accurate diagnosis.

Cluster analysis of computerized visual field and optical coherence tomography-ganglion cell complex defects in high intraocular pressure patients or early stage glaucoma.

PURPOSE: The aim of the study is to evaluate the relationship between functional defects shown by cluster analysis of computerized visual field and anatomic defects from optical coherence tomography-ganglion cell complex examination in ocular hypertension or eyes affected by glaucoma. METHODS: 205 eyes affected by ocular hypertension (intraocular pressure > 22 mmHg) or early stage glaucoma were enrolled. The age of the patients ranged from 26 to 87 years (average: 61.83 ± 1.54 years). Computerized 30° visual field (Octopus G1x Dynamic strategy) and optical coherence tomography-ganglion cell complex (I-Vue Optovue) analyses were performed for each eye selected; 68 eyes were tested and retested from two to seven times for a total of 320 visual fields and 320 optical coherence tomography-ganglion cell complex examinations. The visual field was considered abnormal with a mean defect < -2 and loss variance > 6. The optical coherence tomography-ganglion cell complex was considered abnormal with a significant focal loss volume (p < 5%) and/or a significant thinning of total, superior, or inferior thickness (p < 5%). Four different groups of examinations were created according to the results of visual field and ganglion cell complex: normal visual field and normal ganglion cell complex (group 1), abnormal visual field and abnormal ganglion cell complex (group 2), normal visual field and abnormal ganglion cell complex (group 3), and abnormal visual field and normal ganglion cell complex (group 4). The cluster analysis of visual fields (EyeSuite software Interzeag CH) was performed only in the visual field of group 3, and the correlation between cluster values and topographical changes at optical coherence tomography-ganglion cell complex was analyzed. RESULTS: The results of the ganglion cell complex and visual field examinations matched 247 (77.19%) times. In 143 cases, the examinations belonged to group 1, in 104 to group 2, in 23 to group 3, and, finally, in 50 to group 4. The visual field cluster analysis performed on group 3 showed that the correlation between optical coherence tomography-ganglion cell complex and visual field cluster analysis defects was 100% (both the exams altered). In 72% of them, there was also a topographical correspondence between the visual field and optical coherence tomography-ganglion cell complex defects. CONCLUSION: In the early stages of glaucoma, the visual field cluster analysis seems to be useful to detect some focal defects that can be otherwise underestimated when globally considering the visual field. In group 3, where the conventional analysis of visual field was normal while the optical coherence tomography-ganglion cell complex exam was abnormal, the visual field cluster analysis showed a topographical correlation with optical coherence tomography-ganglion cell complex defects in more than 70% of the examinations performed. In addition, the patients with abnormal visual field and normal optical coherence tomography-ganglion cell complex were older than those with normal visual field and abnormal optical coherence tomography-ganglion cell complex (66.44 ± 3.51 vs 57.04 ± 5.96 years, p < 0.001 (0.0002)). These results confirm that the reliability of a visual field examination is subjective and decreases with age because of its difficulty and the personal compliance of the patient toward this examination.

Thinning rates of retinal nerve layer and ganglion cell-inner plexiform layer in various stages of normal tension glaucoma.

AIMS: To compare the changes in the macular retinal nerve fibre layer (mRNFL), macular ganglion cell layer and inner plexiform layer (mGCIPL), and circumpapillary retinal nerve fibre layer (cpRNFL) in various stages of normal tension glaucoma (NTG) using spectral domain optical coherence tomography. METHODS: Eyes with NTG (n=218) were assigned into three groups based on initial mean deviation (MD) as follows: mild (MD>-6 dB), moderate (-6 dB≥MD≥-12 dB) and severe (-12 dB>MD>-20 dB). Annual rates of change in mRNFL, mGCIPL and cpRNFL thickness were calculated by linear regression analysis. RESULTS: Age, gender, spherical equivalent, and average intraocular pressure during follow-up were not significantly different among the three groups. There were significant differences in the mRNFL, mGCIPL and cpRNFL among the three groups at baseline (p<0.0001 in all sectors except for the mRNFL in the superonasal sector). The average thinning rates of the mRNFL, mGCIPL and cpRNFL were -0.38±0.32 µm/year, -0.62±0.46 µm/year and -0.86±0.83 µm/year, respectively. No significant difference in the rates of change in the mRNFL and mGCIPL were found among the groups in any sector. However, there was a significant difference in the rate of change in the cpRNFL among the groups (in all sectors: p<0.0001). CONCLUSIONS: Changes in the mRNFL and mGCIPL can reflect the progression of NTG even in its advanced stage. However, careful interpretation of changes in the cpRNFL in the advanced stage of glaucoma is warranted due to a potential floor effect.

Comparison of a commercial spectral-domain OCT and swept-source OCT based on an angiography scan for measuring circumpapillary retinal nerve fibre layer thickness.

BACKGROUND/AIMS: To assess the agreement in measuring retinal nerve fibre layer (RNFL) thickness between spectral-domain (SD; Cirrus HD, Carl Zeiss Meditec, USA) optical coherence tomography (OCT) and swept-source (SS; Plex Elite 9000, Carl Zeiss Meditec) OCT using an OCT angiography (OCTA) scanning protocol. METHODS: 57 participants (12 glaucomatous, 8 ocular hypertensive and 74 normal eyes) were scanned with two OCT instruments by a single experienced operator on the same day. Circumpapillary RNFL thicknesses were automatically segmented for SD-OCT and manually segmented for SS-OCTA scans. Agreement of global RNFL thickness, as well as average thickness in four quadrants was assessed using intraclass correlation coefficients (ICCs). RESULTS: There was excellent agreement in the inferior and superior quadrants and the global (all ICC >0.90), followed by good agreement in the temporal (ICC=0.79) and nasal (ICC=0.73) quadrants. The ICC values were similar in the subgroups except within the ocular hypertension group, where the nasal quadrant was less agreeable (ICC=0.31). SS-OCTA-derived RNFL thickness was on average 3 µm thicker than SD-OCT, particularly in the nasal (69.7±11.5 µm vs 66.3±9.3 µm; p<0.001) and temporal (75.6±13.7 µm vs 67.9±12.3 µm; p<0.001) quadrants. CONCLUSIONS: RNFL measurements taken with SS-OCTA have good-to-excellent agreement with SD-OCT, which suggests that the RNFL thickness can be sufficiently extracted from wide-field OCTA scans.

Schiotz Scleral Intraocular Pressure Readings Predict Goldmann Applanation Readings Better Than Rebound Tonometry.

PURPOSE: To study the agreement between scleral intraocular pressure (IOP) measurements using the Schiotz, Icare, and Icare PRO tonometers versus Goldmann applanation tonometer (GAT) in eyes with nonscarred corneas. METHODS: This cross-sectional study included 83 eyes of 55 subjects. The order of IOP estimation was the corneal GAT, followed by ICare, ICare PRO, and Schiotz on the corneal and temporal sclera. The agreement between different tonometers and the 95% limits of agreement (LoA) were assessed using Bland-Altman plots. The repeated measures correlation coefficient was calculated between GAT IOP and scleral Schiotz IOP, and the 95% confidence intervals were calculated by the bootstrap method. The linear mixed effects model was used (adjusted for both eyes of the subjects) to generate an equation to predict GAT IOP from scleral Schiotz IOP. The prediction model was validated with new data from 60 eyes. Statistical analyses were performed using "R" software (version 3.3.2). RESULTS: Comparing the scleral IOP measurements, the mean IOP difference (95% LoA) was the lowest with Schiotz, underestimating by -1.21 mm Hg (7.32, -9.74). Both ICare and ICare PRO significantly overestimated GAT IOP: ICare, 24.6 mm Hg (53.2, -3.97); and ICare PRO, 21.56 mm Hg (52.9, -9.79). The correlation coefficient between scleral Schiotz and GAT IOP was 0.92 (95% bootstrap confidence interval: 0.89, 98). The derived predictive equation was (Equation is included in full-text article.). The mean difference between the predicted GAT IOP and the actual GAT IOP was 0.96 mm Hg with narrow LoA (+1.79, -3.71), validating the prediction model. CONCLUSIONS: Among the tonometers tested, the scleral IOP measurements with Schiotz had the best agreement with the GAT although LoA were wide. The predictive equation may have great potential to predict GAT IOP from scleral IOP readings in eyes with scarred/prosthetic corneas.

Insidious-onset, non-wheezing carteolol-induced asthma in an atopic patient without asthma history.

Carteolol, a non-selective beta-antagonist with a potential risk of severe bronchial constriction in patients with asthma, is one of the most commonly prescribed medication for managing ocular pressure in glaucoma. We present a case of a 24-year-old woman with a history of atopy but no known asthma who presented an insidious onset of clinical manifestations compatible with drug-induced asthma after the initiation of carteolol for ocular hypertension control. The patient developed progressive chest tightness and dyspnoea for 2 months before the pulmonary function test revealed a positive bronchoprovocation response. She reported significant improvement of respiratory symptoms within 2 weeks after the discontinuation of carteolol, and a negative provocation response was later confirmed by repeat pulmonary function test. In conclusion, eye drops with non-selective beta-antagonising effect can induce asthmatic symptoms in patients without a previous diagnosis of asthma and should be administered with caution in patients with associated risk factors.