Nicotinamide provides neuroprotection in glaucoma by protecting against mitochondrial and metabolic dysfunction.

Nicotinamide adenine dinucleotide (NAD) is a REDOX cofactor and metabolite essential for neuronal survival. Glaucoma is a common neurodegenerative disease in which neuronal levels of NAD decline. We assess the effects of nicotinamide (a precursor to NAD) on retinal ganglion cells (the affected neuron in glaucoma) in normal physiological conditions and across a range of glaucoma relevant insults including mitochondrial stress and axon degenerative insults. We demonstrate retinal ganglion cell somal, axonal, and dendritic neuroprotection by nicotinamide in rodent models which represent isolated ocular hypertensive, axon degenerative, and mitochondrial degenerative insults. We performed metabolomics enriched for small molecular weight metabolites for the retina, optic nerve, and superior colliculus which demonstrates that ocular hypertension induces widespread metabolic disruption, including consistent changes to α-ketoglutaric acid, creatine/creatinine, homocysteine, and glycerophosphocholine. This metabolic disruption is prevented by nicotinamide. Nicotinamide provides further neuroprotective effects by increasing oxidative phosphorylation, buffering and preventing metabolic stress, and increasing mitochondrial size and motility whilst simultaneously dampening action potential firing frequency. These data support continued determination of the utility of long-term nicotinamide treatment as a neuroprotective therapy for human glaucoma

Intraocular pressure : clinical aspects and new measurement methods

Intraocular pressure (IOP) measurement is a routine procedure and a fundament in glaucoma care. Elevated IOP is the main risk factor for glaucoma, and to date, reduction of IOP is the only possible treatment. In a retrospective clinical material, the prevalence of open angle glaucoma was estimated on the west coast of Iceland. IOP measurement and optic nerve head examination were used to capture glaucoma suspects, within the compulsory ophthalmological examination for the prescription of eye glasses. The results were mainly in agreement with a recent prospective study in the same region. This indicated that retrospective data, under certain conditions, may contribute with useful information on the prevalence of glaucoma. However, normal tension glaucoma is underestimated if perimetry and/or fundus photography are not included in the examination. Three studies focused on the measurement of IOP. Goldmann applanation tonometry (GAT) is the standard method. GAT is affected by corneal properties, e.g. central corneal thickness (CCT) and corneal curvature (CC). Refractive surgery changes these properties. This has put focus on how corneal biomechanics translate into tonometric errors and stimulated the development of new methods. As a result, Pascal ® Dynamic Contour Tonometry (PDCT) and Icare® rebound tonometry have been introduced. A method under development by our research group is Applanation Resonance Tonometry (ART). It is based on resonance technology and estimates IOP from continuous measurement of force and contact area. Comparison of PDCT, Icare and GAT in a prospective study showed that the concordance to GAT was close to the limits set by the International Standard Organization (ISO) for PDCT, while Icare was outside the limits. To investigate if laser-assisted subepithelial keratectomy (LASEK) affects tonometry, a study was performed where measurements with GAT, PDCT and ART were obtained before, three and six months after LASEK. The hypothesis was that PDCT and ART would be less affected by LASEK than GAT. The results showed a statistically significant reduction of measured IOP three and six months after LASEK for all tonometry methods. Change in visual acuity and IOP between three and six months suggested a prolonged postoperative process. A servo-controlled prototype (ART servo) was developed. A study was undertaken to assess the agreement of ARTservo and a further developed v manual prototype (ART manual) with GAT. The study design was in accordance with the requirements of the ISO standard for tonometers. ARTmanual fulfilled the precision requirements of the ISO standard. ARTservo did not meet all the requirements of the standard at the highest pressure levels. Four tonometry methods, GAT, PDCT, Icare and ART, were investigated. None of them was independent of both CCT and CC. The inconsistencies in the results emphasize the importance of study design. A meta-analysis comprising healthy eyes (IOP ≤ 21 mmHg) in the three papers, revealed age as an important confounder. In summary, glaucoma prevalence in Iceland was investigated and the results indicated that a retrospective approach can contribute with meaningful information. ART and PDCT had a similar agreement to GAT. ART manual fulfilled the precision requirements set by the ISO-standard, ARTservo and PDCT were close, while Icare was distinctly outside the limits. All tonometry methods were affected by LASEK and no method was completely independent of corneal properties

Intracranial and Intraocular Pressure at the Lamina Cribrosa : Gradient Effects

Purpose of Review: A pressure difference between the intraocular and intracranial compartments at the site of the lamina cribrosa has been hypothesized to have a pathophysiological role in several optic nerve head diseases. This paper reviews the current literature on the translamina cribrosa pressure difference (TLCPD), the associated pressure gradient, and its potential pathophysiological role, as well as the methodology to assess TLCPD. Recent Findings: For normal-tension glaucoma (NTG), initial studies indicated low intracranial pressure (ICP) while recent findings indicate that a reduced ICP is not mandatory. Summary: Data from studies on the elevated TLCPD as a pathophysiological factor of NTG are equivocal. From the identification of potential postural effects on the cerebrospinal fluid (CSF) communication between the intracranial and retrolaminar space, we hypothesize that the missing link could be a dysfunction of an occlusion mechanism of the optic nerve sheath around the optic nerve. In upright posture, this could cause an elevated TLCPD even with normal ICP and we suggest that this should be investigated as a pathophysiological component in NTG patients

Outcomes of iStent inject versus kahook dual blade surgery in glaucoma patients undergoing cataract surgery

Précis: iStent Inject implantation (iStent) or Kahook Dual Blade goniotomy (KDB) in combination with phacoemulsification have a similar IOP-lowering effect in all stages of glaucoma, and medications are significantly reduced, especially after KDB. PURPOSE: To compare the 2-year efficacy and safety of iStent or KDB in combination with phacoemulsification in eyes with mild to advanced open angle glaucoma. METHODS: A retrospective chart review of 153 patients that received iStent or KDB in combination with phacoemulsification at a single center between March 2019 and August 2020. The main outcome parameters at 2 years were: (1) intraocular pressure (IOP)-reduction ≥20%, with a postoperative IOP ≤18 mm Hg, and (2) a reduction of ≥1 medication. Results were stratified by glaucoma grade. RESULTS: After 2 years, mean IOP was reduced from 20.3±6.1 to 14.2±4.1 mm Hg in the phaco-iStent group ( P <0.001) and from 20.1±6.1 to 14.7±3.6 mm Hg in the phaco-KDB group ( P <0.001). The mean number of medications was reduced from 3.0±0.9 to 2.6±1.1 in the Phaco-iStent group ( P =0.001) and from 2.3±1.0 to 1.5±1.3 in the Phaco-KDB group ( P <0.001). Success regarding IOP-reduction ≥20% with a postoperative IOP ≤18 mm Hg was met by 46% in the phaco-iStent group and by 51% in the phaco-KDB group. A reduction of ≥1 medication was met by 32% in the phaco-iStent group and by 53% in the phaco-KDB group ( P =0.013). Eyes with mild to moderate and advanced glaucoma responded equally well to the success criteria. CONCLUSIONS: iStent and KDB, in combination with phacoemulsification, both lowered IOP effectively in all stages of glaucoma. More medications were reduced after KDB, suggesting that it may be a more effective procedure compared with iStent

Kahook dual-blade goniotomy with and without phacoemulsification in medically uncontrolled glaucoma

Purpose: To evaluate the 2-year efficacy and safety of Kahook dual-blade (KDB) goniotomy in patients with medically uncontrolled glaucoma. Methods: This was a retrospective case-series study of 90 consecutive patients with primary open-angle glaucoma (POAG) or pseudoexfoliation glaucoma (PEXG) that underwent KDB goniotomy alone (KDB-alone group) or KDB goniotomy in combination with phacoemulsification (KDB-phaco group) during 2019–2020. All patients were uncontrolled on three or more medications. Surgical success was defined as an IOP reduction ≥20% and/or a reduction of one or more medications at 24 months. We also report IOP levels and number of medications from baseline to 24 months, as well as the need for further glaucoma interventions. Results: At 24 months, mean IOP had reduced from 24.8±8.3 to 15.0±5.3 mmHg in the KDB-alone group (P<0.001) and from 22.3 ±5.8 to 13.9±3.0 mmHg in the KDB-phaco group (P<0.001). Medications had reduced from 3.5±0.6 to 3.1±0.9 in the KDB-alone group (P=0.047) and from 3.3±0.5 to 2.3±1.1 in the KDB-phaco group (P<0.001). An IOP reduction ≥20% and/or a reduction with one or more medications was achieved by 47% of eyes in the KDB-alone group and by 76% of eyes in the KDB-phaco group. Eyes with PEXG and POAG responded equally well to the success criteria. During the 24-month follow-up, additional glaucoma surgery or transscleral photocoagulation was performed in 28% of eyes in the KDB-alone group and in 12% of eyes in the KDB-phaco group. Conclusion: In patients with medically uncontrolled glaucoma, KDB had a significant IOP-lowering effect after 24 months, but success rates were higher when KDB was performed in combination with cataract surgery compared to stand-alone treatment

Can postoperative dexamethasone nanoparticle eye drops replace mitomycin C in trabeculectomy?

Purpose: Compare (a) nonmitomycin C (MMC) trabeculectomy and 1.5% dexamethasone nanoparticle (DexNP) eye drops postoperatively with (b) trabeculectomy with MMC and Maxidex® eye drops postoperatively. Methods: Randomized prospective single masked clinical trial with 20 patients with primary open‐angle glaucoma undergoing primary trabeculectomy. The study group consisted of 10 patients without MMC intraoperatively and postoperative DexNP eye drops, and the control group consisted of 10 patients treated with MMC intraoperatively and postoperative Maxidex®. The drops were tapered out over 8 weeks. The main outcome measures were as follows: rates of complete success, that is intraocular pressure (IOP) within target pressures at different time‐points without IOP‐lowering medication, or reoperation. Secondary outcome measures included the following: relative success rate (with IOP‐lowering medications), number of glaucoma medications and reoperations. Patients were followed for 36 months. Results: Both groups showed similar postoperative course and IOP reduction. Intraocular pressures (IOPs) in the DexNP group and in the control group were 25.6 and 24.4 mmHg, respectively, at baseline. Intraocular pressures (IOPs) were reduced to 13.2 and 14.5 mmHg at 12 months, 11.7 and 12.6 mmHg at 24 months and 11.7 and 12.1 mmHg at 36 months, respectively. There were no statistically significant differences between the groups in absolute (p = 0.36) or relative (p = 1.0) success rates, number of medications (p = 0.71) or reoperations (p = 1.0) between the groups at any time‐point. Conclusions: DexNP eye drops are effective postoperative treatment following trabeculectomy. The potent anti‐inflammatory and antifibrotic effect of DexNP may offer an alternative to mitomycin C in glaucoma surgery

Wally and the Major [picture] : modern hazard /

Part of the Stan Cross Archive of cartoons and drawings, 1912-1974.; Inscription: "4808 Fri Dec 23 Modern Hazard"--In Ink, right margin; "4731"--In Ink, upper right corner; "5"--In pencil, upper left corner.; Also available in an electronic version via the internet at: http://nla.gov.au/nla.pic-vn4301760

The glaucoma intensive treatment study : interim results from an ongoing longitudinal randomized clinical trial

Funding text Financial support was provided through regional agreements between Lund University and Skane Regional Council (ALF), and between Umea University and V€asterbotten County Council and also by grants from the Swedish Society for medical research, Knut and Alice Wallenbergs foundation, Cronqvist foundation, € Ogonfonden, Swedish medical society foundation, Foundation for visually impaired in former Malm€ohus county, King Gustav V and Queen Victoria’s freemason foundation, foundations and donations administered by Skane University Hospital, Crown Princess Margareta´s foundation, Margit and Kjell Stolz Foundation, Herman J€arnhardt foundation, Ingrid Nordmark’s foundation and Insamlingsstiftelserna vid Umea universitet. None of the supporting organizations had any role in the design or conduct of the research. Publisher Copyright: © 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.Purpose: The aim of the study was to determine the perimetric rate of glaucoma progression in the ongoing Glaucoma Intensive Treatment Study (GITS) after 3 years of follow-up. Design: This is a randomized, two-centre, prospective open-labelled treatment trial for open-angle glaucoma (OAG). Participants: The participants of this study were treatment-naive patients with newly diagnosed OAG, aged 46–78 years, with early to moderate glaucomatous visual field loss scheduled to be followed for 5 years within the study. Methods: Patients were randomized to initial treatment with either topical monotherapy or with an intensive approach using drugs from three different classes, plus 360° laser trabeculoplasty. Changes in treatment were allowed. Standard automated perimetry and tonometry were performed and side-effects documented. All results are presented using intention-to-treat analysis. Results: A total of 242 patients were randomized. After 3 years of follow-up, eight patients were lost to follow-up, six of whom were deceased. The median untreated baseline intraocular pressure (IOP) was 24 mmHg in both arms. The median IOP was almost constant over the 3 years of follow-up: ≈17 mmHg in the mono-arm and ≈14 mmHg in the multi-treatment arm. Treatment was intensified in 42% of the mono-treated patients and in 7% of the multi-treated patients. Treatment was reduced in 13% of the multi-treated patients. The median perimetric rate of progression was −0.5%/year in the mono-treated group and −0.1%/year in the multi-treated group (p = 0.03). Conclusion: The rate of disease progression was significantly slower in the multi-treated patients than in the mono-treated patients. Further follow-up will show whether this difference is sustained over time.Peer reviewe

Normal-Tension Glaucoma Has Normal Intracranial Pressure : A Prospective Study of Intracranial Pressure and Intraocular Pressure in Different Body Positions

PURPOSE: To test the hypothesis that normal-tension glaucoma (NTG) is caused by an increased pressure difference across the lamina cribrosa (LC) related to a low intracranial pressure (ICP). DESIGN: Prospective case-control study. PARTICIPANTS: Thirteen NTG patients (9 women; median 71 [range: 56-83] years) were recruited for investigation with the same protocol as 11 healthy volunteers (8 women; 47 [30-59] years). A larger control group (n = 51; 30 women; 68 [30-81] years) was used only for ICP comparison in supine position. METHODS: ICP and intraocular pressure (IOP) were simultaneously measured in supine, sitting, and 9° head-down tilt (HDT) positions. Trans-lamina cribrosa pressure difference (TLCPD) was calculated using ICP and IOP together with geometric distances estimated from magnetic resonance imaging to adjust for hydrostatic effects. MAIN OUTCOME MEASURES: ICP, IOP, and TLCPD in different body positions. RESULTS: Between NTG patients and healthy volunteers, there were no differences in ICP, IOP, or TLCPD in supine, sitting, or HDT (P ≥ 0.11), except for IOP in HDT (P = 0.04). There was no correlation between visual field defect and TLCPD, IOP, or ICP and in any body position (P ≥ 0.39). Mean ICP in supine was 10.3 mmHg (SD = 2.7) in the NTG group (n = 13) and 11.3 (2.2) mmHg in the larger control group (n = 51) (P = 0.24). CONCLUSIONS: There was no evidence of reduced ICP in NTG patients as compared with healthy controls, either in supine or in upright position. Consequently, the hypothesis that NTG is caused by an elevated TLCPD from low ICP was not supported

Intraocular Pressure Decrease Does Not Affect Blood Flow Rate of Ophthalmic Artery in Ocular Hypertension

PURPOSE: To investigate if decrease of IOP affects the volumetric blood flow rate in the ophthalmic artery (OA) in patients with previously untreated ocular hypertension. METHODS: Subjects with untreated ocular hypertension (n = 30; mean age 67 +/- 8 years; 14 females) underwent ophthalmologic examination and a 3-Tesla magnetic resonance imaging investigation. The magnetic resonance imaging included three-dimensional high-resolution phase-contrast magnetic resonance imaging to measure the OA blood flow rate. The subjects received latanoprost once daily in the eye with higher pressure, the untreated eye served as control. The same measurements were repeated approximately 1 week later. RESULTS: The mean OA blood flow rate before and after treatment was 12.4 +/- 4.4 and 12.4 +/- 4.6 mL/min in the treated eye (mean +/- SD; P = 0.92) and 13.5 +/- 5.2 and 13.4 +/- 4.1 mL/min in the control eye (P = 0.92). There was no significant difference between the treated and control eye regarding blood flow rate before (P = 0.13) or after treatment (P = 0.18), or change in blood flow rate after treatment (0.1 +/- 3.1 vs.-0.1 +/- 4.0 mL/min, P = 0.84). Latanoprost decreased the IOP by 7.2 +/- 3.1 mm Hg in the treated eye (P < 0.01). CONCLUSIONS: The results indicate that a significant lowering of IOP does not affect the blood flow rate of the OA in ocular hypertension subjects. The ability to maintain blood supply to the eye independent of the IOP could be a protective mechanism in preserving vision in subjects with ocular hypertension