Preservative-Free Bimatoprost 0.01% Ophthalmic Gel for Glaucoma Therapy: A Phase III Randomized Controlled Trial.

PRCIS: Noninferiority of efficacy was demonstrated for a preservative-free bimatoprost 0.01% compared with BAK-containing bimatoprost 0.01% following a 12-week treatment period in patients with open angle glaucoma or ocular hypertension. Improved tolerability, in particular conjunctival hyperemia, was also observed. PURPOSE: To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of a preservative-free bimatoprost 0.01% ophthalmic gel (PFB 0.01% gel) compared with preserved bimatoprost 0.01% (PB 0.01%). DESIGN: Phase III, international, multicenter, randomized, 2-parallel group, investigator-masked, 3-month treatment duration. METHODS: Patients with glaucoma or ocular hypertension were randomized after a 7-week run-in/washout period to receive once-daily PFB 0.01% gel (n=236) or PB 0.01% (n=249) for 3 months. The primary efficacy measure was changed from baseline in IOP at week 12. Safety measures included adverse events (AEs) and assessment of conjunctival hyperemia. RESULTS: The mean changes from baseline in IOP at week 12 in the PFB 0.01% gel and PB 0.01% were -9.72±2.97 and -9.47±3.06 mm Hg, respectively, at 8 am , -9.41±3.03 and -9.19±3.12 mm Hg at 10 am , and -8.99±3.36 and -8.54±3.44 mm Hg at 4 pm . Noninferiority of PFB 0.01% gel to PB 0.01% was demonstrated at week 12 based on predetermined criteria (upper 95% CI margin of 1.5 mmHg at all time points). The most frequently reported AE was conjunctival hyperemia; 13 (5.5%) patients with PFB 0.01% gel and 17 (6.8%) patients with PB 0.01%. The percentage of patients experiencing a worsening from baseline in conjunctival hyperemia score was lower with PFB 0.01% gel compared to PB 0.01% at week 6 (20.1% vs. 29.3%, respectively) and week 12 (18.3% vs. 30.4%, respectively). CONCLUSIONS: PFB 0.01% ophthalmic gel has the same efficacy in lowering IOP as PB 0.01% and demonstrated less aggravation of conjunctival hyperemia at weeks 6 and 12.

Bézier curves as a total approach to measure the upper lid contour: redefining clinical outcomes in palpebral surgery.

AIMS: To define and quantify the upper lid contour by adapting Bézier curves with a newly developed software in normal subjects, assessing their reliability. METHODS: Fifty eyes of 50 healthy patients with no ocular pathology were included in this study from October 2020 to November 2020. All measurements were performed on Bézier curves adjusted to the upper lid contour. An original software was used to measure the radial and vertical midpupil-to-lid margin distances (MPLD), temporal-to-nasal (T/N) ratios, contour peak location and grade of superposition (GS) and asymmetry (GA) indexes. We calculated differences in the variables measured regarding age, gender or the side of the eye being assessed. RESULTS: The mean Bézier curve showed an excellent level of inter-rater reliability (intraclass correlation coefficient of 0.99). The median GS index of each eyelid to the mean Bézier curve was 95.4%, 8.5 IQR, and the median GA index was 3%, 3.4 IQR. The mean contour peak location was -0.35 mm, SD 0.45. Overall, the mean central MPLD was 4.1 mm, SD 0.6. No significant differences were found between male and female patients in variables derived from Bézier curves. CONCLUSION: Bézier curves may become a very useful tool for the assessment of upper lid contour, contour peak and symmetry. GS and GA indexes, along with the T/N area ratio are potential outcomes for this purpose. All current variables can be obtained just from one single Bézier curve measurement. Our results offer an in-depth exhaustive description of these variables and their distribution in the normal population.

Müllerotomy with anterior graded Müller muscle disinsertion for Graves upper eyelid retraction: validation of surgical outcomes using Bézier curves.

PURPOSE: To assess with Bézier curves the outcomes of Müllerotomy with anterior graded Müller muscle disinsertion for the treatment of Graves upper eyelid retraction (UER). METHODS: Eighty-six eyelids of 52 inactive GO patients operated from November 2018 to June 2021 were included in this study. All measurements were performed on Bézier curves adjusted to the upper lid contour with a previously validated algorithm. Lid contour was classified regarding grade of superposition (GS) as excellent (GS > 90%), good (GS 85-90%) or poor (< 85%). Surgical success was defined as complete or partial if postoperative grade of asymmetry was < 10% with an excellent or good lid contour, respectively. RESULTS: The mean age was 51 ± 10.4 years with a range from 31 to 78 years and a mean follow-up of 14.4 ± 7.4 months. There was a significant improvement of median GS (p < 0.0001) from preoperative (74.3%; 10.7 IQR) to postoperative values (91.7%; 6.3 IQR). A normalization of postoperative contour peak (- 0.69; 1.27 SD) and MPLD90 (4.2 mm; 0.8 SD) was noticed (p < 0.0001). Postoperative lid contour was excellent in 62 (72%), good in 16 (19%) and poor in 8 eyelids (9%). Surgical success was achieved in 42 patients (81%), from which 34 (81%) were complete. Reintervention was required in 14 eyelids (16%). CONCLUSIONS: Measuring surgical outcomes with Bézier curves allows an automated, complete and objective assessment, giving more consistency to our data compared to previous reports. Müllerotomy with graded Müller muscle disinsertion is a safe and effective procedure for Graves UER, offering predictable results.

Postoperative drift and dose-response of strabismus surgery in thyroid eye disease: predicting desired outcomes with intraoperative adjustable sutures.

OBJECTIVE: To report outcomes of strabismus surgery in thyroid eye disease using intraoperative bow-knot adjustable sutures under topical anaesthesia and calculate prediction models for surgical correction and postoperative drift depending on surgical dose-response. METHODS: We retrospectively reviewed patients operated on from 2016 to 2021. A satisfactory outcome was defined as no diplopia with maintenance of vertical (<5 PD) and horizontal (<10 PD) stable alignment at primary gaze. Subjective diplopia corrected with prisms within successful motor alignment was defined as a fair result. Otherwise, the result was considered to be poor. RESULTS: A total of 73 patients were included (60 females, 82%). Mean preoperative horizontal and vertical deviations were 26.9 PD (19.1 SD), and 11.8 PD (7.6 SD), respectively. Mean horizontal drift was -3.2 PD (5.2 SD), whereas mean vertical drift was -3.4 PD (3.3 SD). A linear regression established a dose-response of 2.37 PD/mm for each medial rectus recession (p < 0.0001; r2 = 0.777) and 3.75 PD/mm for unilateral inferior rectus recession (p < 0.0001; r2 = 0.922). Final success rate was satisfactory in 62 patients (85%), fair in 7 patients (10%), and poor in 4 patients (5%). CONCLUSIONS: Muscle recession with intraoperative adjustable sutures is effective for the treatment of thyroid eye disease strabismus. Predictable dose-responses could be achieved with a drift toward overcorrection. Undercorrection proportional to the planned surgical dose should be the immediate postoperative target of choice. Other variables such as orbital decompression and concurrent vertical and horizontal surgery do not correlate with dose-response and postoperative drift. However, further studies are necessary to validate our findings.

Changes in eyelid position after glaucoma filtering surgery.

BACKGROUND: While ptosis is a well-known consequence of glaucoma surgery, some isolated case reports point to the possibility of upper eyelid retraction occurring after glaucoma surgery. This study aims to analyze the occurrence of ptosis and eyelid retraction after glaucoma surgery and to evaluate factors contributing to these palpebral fissure changes. METHODS: Cross-sectional study including 100 eyes of 100 patients that had undergone unilateral glaucoma surgery. Upper eyelid height in the operated eye was measured by digital photography and compared with the fellow, non-operated eye. The main outcome was to determine if ptosis or retraction occurred in the operated eye in comparison with the fellow eye. The secondary outcome was to determine if any variable was associated with ptosis or retraction. A clinically significant difference (either toward ptosis or retraction) was defined as a difference ≥1 mm between both eyes. RESULTS: Of 100 eyes included 81 (81%) showed no change in eyelid height (-0.133 mm ± 0.496), 11 (11%) showed ptosis (-1.348 mm ± 0.387) and 8 eyes (8%) showed retraction (1.705 ± 0.634). A statistically significant relation was found between ptosis and pseudoexfoliation glaucoma (p = 0.003). A trend toward lower postoperative IOP and higher conjunctival blebs was found in eyes with postoperative eyelid retraction. CONCLUSIONS: Eyelid retraction was present in 8% of patients and ptosis in 11%. Patients with eyelid retraction showed around a 3 mmHg lower postoperative IOP than eyes without retraction. The presence of pseudoexfoliation may be a risk factor for this complication. A prospective study with a large number of patients would be required to confirm these results.

Recommendations for ophthalmologic practice during the easing of COVID-19 control measures.

In the context of the COVID-19 pandemic, this paper provides recommendations for medical eye care during the easing of control measures after lockdown. The guidelines presented are based on a literature review and consensus among all Spanish Ophthalmology Societies regarding protection measures recommended for the ophthalmologic care of patients with or without confirmed COVID-19 in outpatient, inpatient, emergency and surgery settings. We recommend that all measures be adapted to the circumstances and availability of personal protective equipment at each centre and also highlight the need to periodically update recommendations as we may need to readopt more restrictive measures depending on the local epidemiology of the virus. These guidelines are designed to avoid the transmission of SARS-CoV-2 among both patients and healthcare staff as we gradually return to normal medical practice, to prevent postoperative complications and try to reduce possible deficiencies in the diagnosis, treatment and follow-up of the ophthalmic diseases. With this update (5th ) the Spanish Society of Ophthalmology is placed as one of the major ophthalmology societies providing periodic and systematized recommendations for ophthalmic care during the COVID-19 pandemic.

Enhanced Depth Imaging Optical Coherence Tomography Technology Reveals a Significant Association Between Optic Nerve Drusen Anterior Displacement and Retinal Nerve Fiber Layer Thinning Over Time.

BACKGROUND: Optic disc drusen (ODD) are a dynamic phenomenon, and their appearance, size, and relative location may change. The purpose of this study is to evaluate and quantify the longitudinal changes of buried ODD with enhanced depth imaging (EDI) optical coherence tomography (OCT) over time. METHODS: ODD were analyzed with Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany) and EDI technology. The peripapillary retinal nerve fiber layer (RNFL) thickness was also measured. The size and depth of ODD were compared between the baseline and study visit (at least 2 years of follow-up), and the changes were correlated with mean RNFL thickness. The repeatability, coefficient of variation, and cutoff values for size and depth on EDI-OCT were calculated. RESULTS: Of 21 previously identified patients with ODD, only 12 patients (21 eyes) met the most recent diagnostic criteria according to the ODD Studies Consortium recommendations for using OCT-EDI technology. The 21 eyes were reanalyzed after a mean period of 44.7 ± 13.2 months (range: 24-71 months). Overall, 132 ODD were evaluated with a mean of 6.1 ± 2.5 ODD per eye and 1.9 ± 1.1 ODD per scan. Overall, we found a significant forward movement of the drusen between visits (P = 0.01). Most drusen (67.4%) moved anteriorly, and in approximately one-third (35.6%), this displacement exceeded the cutoff value (64.28 µm). Furthermore, we found a significant correlation between ODD shallowing and RNFL thinning during the follow-up (P ≤ 0.03; R ≥ 0.370). We did not find any significant changes in size measurements (P = 0.10) over time. CONCLUSIONS: In approximately one-third of buried ODD, a significant anterior movement occurred over 2 years of follow-up, and this movement was associated with significant RNFL thinning. By contrast, no significant change was detected in the size of the buried ODD.

Real-World Clinical Experience With Idebenone in the Treatment of Leber Hereditary Optic Neuropathy.

BACKGROUND: Leber hereditary optic neuropathy (LHON) leads to bilateral central vision loss. In a clinical trial setting, idebenone has been shown to be safe and to provide a trend toward improved visual acuity, but long-term evidence of effectiveness in real-world clinical practice is sparse. METHODS: Open-label, multicenter, retrospective, noncontrolled analysis of long-term visual acuity and safety in 111 LHON patients treated with idebenone (900 mg/day) in an expanded access program. Eligible patients had a confirmed mitochondrial DNA mutation and had experienced the onset of symptoms (most recent eye) within 1 year before enrollment. Data on visual acuity and adverse events were collected as per normal clinical practice. Efficacy was assessed as the proportion of patients with either a clinically relevant recovery (CRR) or a clinically relevant stabilization (CRS) of visual acuity. In the case of CRR, time to and magnitude of recovery over the course of time were also assessed. RESULTS: At time of analysis, 87 patients had provided longitudinal efficacy data. Average treatment duration was 25.6 months. CRR was observed in 46.0% of patients. Analysis of treatment effect by duration showed that the proportion of patients with recovery and the magnitude of recovery increased with treatment duration. Average gain in best-corrected visual acuity for responders was 0.72 logarithm of the minimal angle of resolution (logMAR), equivalent to more than 7 lines on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Furthermore, 50% of patients who had a visual acuity below 1.0 logMAR in at least one eye at initiation of treatment successfully maintained their vision below this threshold by last observation. Idebenone was well tolerated, with most adverse events classified as minor. CONCLUSIONS: These data demonstrate the benefit of idebenone treatment in recovering lost vision and maintaining good residual vision in a real-world setting. Together, these findings indicate that idebenone treatment should be initiated early and be maintained more than 24 months to maximize efficacy. Safety results were consistent with the known safety profile of idebenone.

The role of neuroinflammation in the pathogenesis of glaucoma neurodegeneration.

The chapter is a review enclosed in the volume "Glaucoma: A pancitopatia of the retina and beyond." No cure exists for glaucoma. Knowledge on the molecular and cellular alterations underlying glaucoma neurodegeneration (GL-ND) includes innovative and path-breaking research on neuroinflammation and neuroprotection. A series of events involving immune response (IR), oxidative stress and gene expression are occurring during the glaucoma course. Uveitic glaucoma (UG) is a prevalent acute/chronic complication, in the setting of chronic anterior chamber inflammation. Managing the disease requires a team approach to guarantee better results for eyes and vision. Advances in biomedicine/biotechnology are driving a tremendous revolution in ophthalmology and ophthalmic research. New diagnostic and imaging modalities, constantly refined, enable outstanding criteria for delimiting glaucomatous neurodegeneration. Moreover, biotherapies that may modulate or inhibit the IR must be considered among the first-line for glaucoma neuroprotection. This review offers the readers useful and practical information on the latest updates in this regard.

Recomendaciones para la atención oftalmológica durante el estado de alarma por la pandemia de enfermedad por coronavirus COVID-19 / Recommendations for eye care during the alarm state bythe coronavirus disease pandemic COVID-19

OBJETIVO: Minimizar la exposición al virus SARS-CoV-2, reducir las posibilidades de transmisión cruzada entre pacientes y personal sanitario, y evitar el desarrollo de complicaciones postoperatorias por la atención a pacientes con enfermedades oculares durante la pandemia de Enfermedad por Coronavirus 2019 (COVID-19). MÉTODOS: Elaboración de un documento de revisión del estado del conocimiento sobre COVID-19 y consenso entre diferentes sociedades oftalmológicas españolas y afines, al objeto de proporcionar guías y recomendaciones de máximos recursos primariamente condicionadas por el estado de alerta, confinamiento y distanciamiento social que acontece en España desde el 16 de marzo de 2020. RESULTADOS: Las recomendaciones promoverán la adopción de medidas de actuación y protección para el desarrollo de la actividad asistencial en consultas externas, área quirúrgica y hospitalización, tanto para pacientes no confirmados - asintomáticos y sintomáticos - como confirmados de COVID-19. Deberán ser adaptadas a las circunstancias y disponibilidad de Equipos de Protección Individual (EPI) en cada uno de los Centros y Comunidades Autónomas, debiendo ser actualizadas en función de las fases de la pandemia y de las medidas que adopte el Gobierno de la Nación. CONCLUSIONES: Durante la pandemia COVID-19, la atención a los potenciales riesgos de salud para la población ocasionados por el coronavirus deberá prevalecer sobre la posible progresión de enfermedades oculares comunes. Tanto médicos oftalmólogos como restantes profesionales de la salud ocular deberán asumir una posible progresión de dichas enfermedades ante la imposibilidad de un seguimiento adecuado de los pacientes

OBJECTIVE: Minimize exposure to the SARS-CoV-2, reduce the chances of cross-transmission between patients and healthcare personnel, and prevent the development of postoperative complications from the management of patients with eye diseases during the 2019 coronavirus disease pandemic (COVID -19). METHODS: COVID-19 literature review and consensus establishment between different Spanish ophthalmology societies in order to provide guidelines and recommendations of máximum resources primarily conditioned by the state of alert, confinement and social distancing that occurs in Spain since March 16, 2020. Results: The recommendations will promote the adoption of action and protection measures for eye care in outpatient clinics, surgical areas and hospitalization, for unconfirmed (asymptomatic and symptomatic) and confirmed COVID-19 patients. Measures must be adapted to the circumstances and availability of Personal Protective Equipment (PPE) in each of the centers and Autonomous Communities, which will be updated according to the pandemic phases and the measures adopted by the Spanish Government. Conclusions: During the COVID-19 pandemic, attention to the potential health risks to the population caused by coronavirus should prevail over the possible progression of the common eye diseases. Ophthalmologists and other eye care professionals must assume a possible progression of these diseases due to the impossibility of adequate patient follow-up

Bilateral decompression retinopathy after deep sclerectomy with mitomycin C in a child with tubulointerstitial nephritis and uveitis syndrome.

INTRODUCTION: To report the first case of bilateral ocular decompression retinopathy after uneventful non-perforating deep sclerectomy with mitomycin C in a child with tubulointerstitial nephritis and uveitis syndrome. CASE DESCRIPTION: An 8-year-old girl affected by tubulointerstitial nephritis and uveitis syndrome developed ocular hypertension (45 mmHg in the right eye and 42 mmHg in the left eye) associated with recurrent episodes of uveitis and chronic use of steroids despite maximum hypotensive medical treatment. Bilateral non-perforating deep sclerectomy with mitomycin C (0.2 mg/mL, 1 min) was performed under general anesthesia without complications. The first postoperative day, the visual acuity was reduced to 0.6 in the right eye and 0.05 in the left eye and the intraocular pressure was 3 mmHg in both eyes. Fundoscopy revealed bilateral optic nerve swelling and diffuse retinal hemorrhages, some of them with scattered-white centers. About 2 months after surgery, the visual acuity was normal and the fundus examination showed complete resolution. CONCLUSION: The ocular decompression retinopathy is an uncommon complication after non-perforating deep sclerectomy. This is the first case of bilateral ocular decompression retinopathy reported after non-perforating deep sclerectomy in a child with ocular hypertension secondary to recurrent uveitis and chronic use of steroids associated with tubulointerstitial nephritis and uveitis syndrome.

Reduced Peripapillary and Macular Vessel Density in Unilateral Postgeniculate Lesions With Retrograde Transsynaptic Degeneration.

BACKGROUND: Retrograde transsynaptic degeneration (RTSD) of the retinal ganglion cells and retinal nerve fiber layer after postgeniculate injury has been well documented, but to the best of our knowledge, associated retinal microvascular changes have not been examined. The purpose of our study was to assess vessel density (VD) at macular and peripapillary regions in patients with RTSD. METHODS: Cross-sectional study including 16 patients with homonymous visual field defects secondary to unilateral postgeniculate visual pathway injury and 18 age-matched controls. All participants were examined with AngioVue optical coherence tomography angiography to measure the peripapillary vessel density and macular vessel density (pVD/mVD) as well as the peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell complex (GCC) thicknesses. The pRNFL and macular ganglion cell-inner plexiform layer (GCIPL) thicknesses also were evaluated using Cirrus OCT. A normalized asymmetry score (NAS) was calculated for GCIPL and GCC thickness, and mVD. RESULTS: Average pRNFL and macular GCIPL/GCC thicknesses were significantly thinner in both eyes of patients compared with control eyes (all P ≤ 0.05). Eight patients (50%), who showed a RTSD of the GCIPL map, had a relative thinning of the GCIPL/GCC ipsilateral to the brain lesion in both eyes (represented by a positive GCIPL-NAS/GCC-NAS). The mean pVD and mVD also were significantly reduced in patients (all P ≤ 0.05). There was a strong correlation between GCIPL-NAS/GCC-NAS and mVD-NAS index in both eyes (all r > 0.7, P = 0.001). Furthermore, there was a similar spatial pattern of damage for the macular GCC thickness and VD values. CONCLUSIONS: We demonstrated a significant VD decrease in peripapillary and macular areas of patients with RTSD because of postgeniculate lesions. The structural and microvascular asymmetry indexes were significantly correlated. These findings provide new insights regarding transsynaptic degeneration of the visual system.

The EX-PRESS glaucoma shunt versus nonpenetrating deep sclerectomy with Esnoper implant in combined surgery for open-angle glaucoma: a prospective randomized study.

PURPOSE: To report 1-year treatment outcomes of P50 EX-PRESS implant versus nonpenetrating deep sclerectomy (NPDS) with Esnoper V2000 combined with phacoemulsification. DESIGN: Randomized, prospective and multicentre clinical trial. METHODS: Settings: Six clinical centres. POPULATION: Patients 54-89 years of age without previous filtering surgery with cataract and glaucoma who required lower levels of intraocular pressure (IOP). INTERVENTIONS: Phaco-EX-PRESS P50 or Phaco-NPDS with Esnoper V2000, both groups with mitomycin C (0.2 mg/ml for 2 min). MAIN OUTCOME MEASURES: IOP, complete success rate (IOP: ≥6 and ≤18 mmHg), visual acuity, use of medical therapy and systematic assessment of complications and postoperative interventions. RESULTS: A total of 98 eyes were enrolled, including 50 in the EX-PRESS group and 48 in the NPDS group. At 12 months, IOP (mean ± SD) was 13.9 ± 3.3 mmHg in EX-PRESS group and 13.3 ± 3.6 mmHg in NPDS group (p = 0.38). Success rate was 75% and 80% in EX-PRESS and NPDS groups, respectively (p = 0.53). The number of glaucoma medications (mean ± SD) was 0.2 ± 0.55 in EX-PRESS group and 0.17 ± 0.44 in NPDS group (p = 1.00). The total number of complications was 66 in 35 subjects in EX-PRESS group and 39 in 23 subjects in NPDS group (p = 0.02). The incidence of more than one complication was n = 13 (26%) versus n = 9 (18.8%) in EX-PRESS and NPDS groups, respectively (p = 0.38). The total number of required postoperative interventions was 59 and 26 in EX-PRESS and NPDS groups, respectively (p = 0.01). Visual acuity was similar in both groups at month 12 (p = 0.13). Surgical time (mean ± SD) was 52.6 ± 13.6 min in EX-PRESS group and 63.3 ± 19.4 min in NPDS group (p = 0.01). CONCLUSION: Phaco-EX-PRESS surgery had similar success rate compared to Phaco-NPDS during 1 year of follow-up. Both procedures were associated with similar IOP reduction and use of additional medical therapy at 12 months. EX-PRESS surgery required more postoperative interventions and had more complications, but needed less surgical time compared to NPDS.

Lamina cribrosa position and Bruch's membrane opening differences between anterior ischemic optic neuropathy and open-angle glaucoma.

PURPOSE:: To compare the optic nerve head morphology among primary open-angle glaucoma, non-arteritic anterior ischemic optic neuropathy eyes, their fellow healthy eyes and control eyes, using spectral-domain optical coherence tomography with enhanced depth imaging. METHODS:: Observational cross-sectional study including 88 eyes of 68 patients. In this study, 23 non-arteritic anterior ischemic optic neuropathy eyes, 17 fellow unaffected eyes, 25 primary open-angle glaucoma eyes, and 23 age-matched control eyes were included. Peripapillary retinal nerve fiber layer thickness and optic disk area were evaluated. Bruch's membrane opening diameter, optic cup depth, anterior lamina cribrosa depth, and prelaminar tissue thickness were assessed. RESULTS:: Non-arteritic anterior ischemic optic neuropathy and primary open-angle glaucoma eyes had similar visual field mean deviation and peripapillary retinal nerve fiber layer thickness (P = 0.6 and P = 0.56, respectively). Bruch's membrane opening diameter was significantly larger in primary open-angle glaucoma eyes than in control eyes (P = 0.02). Lamina cribrosa and disk cup were deeper in eyes with primary open-angle glaucoma than both control and non-arteritic anterior ischemic optic neuropathy eyes (P < 0.001). Prelaminar tissue thickness was significantly thinner in primary open-angle glaucoma eyes than in non-arteritic anterior ischemic optic neuropathy eyes (P < 0.001). Lamina cribrosa was shallower in both non-arteritic anterior ischemic optic neuropathy and unaffected fellow eyes compared to healthy eyes (P < 0.001 and P = 0.04, respectively). No differences were found in the optic disk area. CONCLUSION:: A forward lamina cribrosa placement and not a smaller disk could be involved in the pathogenesis of non-arteritic anterior ischemic optic neuropathy. A significantly larger Bruch's membrane opening diameter was found in primary open-angle glaucoma eyes compared with control eyes. This issue has clinical implications because Bruch's membrane opening has been considered a stable reference for disk-related measures.

A comparison of two optical coherence tomography-angiography devices in pseudoexfoliation glaucoma versus primary open-angle glaucoma and healthy subjects.

PURPOSE: To compare peripapillary vascular parameters derived from two optical coherence tomography angiography devices in pseudoexfoliation glaucoma, primary open-angle glaucoma, and healthy controls and to evaluate their diagnostic accuracy. METHODS: Observational, cross-sectional study. In total, 20 eyes with pseudoexfoliation glaucoma, 20 primary open-angle glaucoma eyes matched by peripapillary retinal nerve fiber layer thickness, and 20 control eyes were recruited. Participants underwent standard automated perimetry and peripapillary retinal nerve fiber layer analysis by Optovue and Cirrus optical coherence tomography. Vascular parameters provided by Angiovue and Angioplex optical coherence tomography angiography were compared. Their diagnostic accuracy and correlation with structural and functional parameters were assessed. RESULTS: All peripapillary optical coherence tomography angiography vascular parameters were significantly different among groups (all p < 0.05). The whole image capillary density and peripapillary capillary density by Angiovue were significantly lower in pseudoexfoliation glaucoma compared with primary open-angle glaucoma (p = 0.009 and p = 0.001, respectively). Conversely, vascular parameters by Angioplex were not statistically different between primary open-angle glaucoma and pseudoexfoliation glaucoma. A good correlation was found using Angiovue between whole image capillary density and visual field mean deviation (0.758, p < 0.001), peripapillary capillary density and visual field mean deviation (0.729, p = 0.001), and peripapillary capillary density and peripapillary retinal nerve fiber layer thickness in eyes with pseudoexfoliation glaucoma (0.716, p = 0.001). Angiovue parameters showed higher area under the receiver operating characteristic curves than Angioplex to discriminate among groups. CONCLUSION: Only Angiovue detected a significantly lower capillary density in pseudoexfoliation glaucoma compared to primary open-angle glaucoma at similar glaucoma damage. Both, Angiovue and Angioplex demonstrated a decreased capillary density in glaucoma eyes compared to healthy eyes. Furthermore, Angiovue-derived vascular parameters showed better correlation with functional and structural parameters and a higher diagnostic capacity to discriminate among groups compared to Angioplex.

Parental Mosaicism in PAX6 Causes Intra-Familial Variability: Implications for Genetic Counseling of Congenital Aniridia and Microphthalmia.

Mutations in PAX6 are involved in several developmental eye disorders. These disorders have considerable phenotypic variability, ranging from panocular forms of congenital aniridia and microphthalmia to isolated anomalies of the anterior or posterior segment. Here, we describe 3 families with variable inter-generational ocular expression of aniridia, iris coloboma, or microphthalmia, and an unusual transmission of PAX6 mutations from an unaffected or mildly affected parent; all of which raised suspicion of gonosomal mosaicism. We first identified two previously known nonsense mutations and one novel likely pathogenic missense variant in PAX6 in probands by means of targeted NGS. The subsequent segregation analysis by Sanger sequencing evidenced the presence of highly probable mosaic events in paternal blood samples. Mosaicism was further confirmed by droplet digital PCR analysis in several somatic tissues of mosaic fathers. Quantification of the mutant allele fraction in parental samples showed a marked deviation from 50%, with a range between 12 and 29% depending on cell type. Gonosomal mosaicsm was definitively confirmed in one of the families thanks to the availability of a sperm sample from the mosaic father. Thus, the recurrence risk in this family was estimated to be about one-third. This is the first report confirming parental PAX6 mosaicism as a cause of disease recurrence in aniridia and other related phenotypes. In addition, we demonstrated that post-zygotic mosaicism is a frequent and underestimated pathogenic mechanism in aniridia, explaining intra-familial phenotypic variability in many cases. Our findings may have substantial implications for genetic counseling in congenital aniridia. Thus, we also highlight the importance of comprehensive genetic screening of parents for new sporadic cases with aniridia or related developmental eye disease to more accurately assess recurrence risk. In conclusion, somatic and/or gonosomal mosaicism should be taken into consideration as a genetic factor to explain not only families with unaffected parents despite multiple affected children but also variable expressivity, apparent de novo cases, and even uncharacterized cases of aniridia and related developmental eye disorders, apparently lacking PAX6 mutations.