Progression Of Glaucomatous Damage Research Articles

Progression of Early Glaucomatous Damage: Performance of Summary Statistics From Optical Coherence Tomography and Perimetry.

Performance comparison of optical coherence tomography (OCT) and visual field (VF) summary metrics for detecting glaucomatous progression. Thirty healthy control eyes (mean deviation [MD], -1.25 ± 2.03; pattern standard deviation [PSD] , 1.78 ± 0.77) and 91 patient eyes comprised of 54 glaucoma patients and 37 glaucoma suspects (MD, -1.58 ± 1.96; PSD, 2.82 ± 1.92) with a follow-up of at least 1 year formed a group to evaluate progression with event analyses (P-Event). A subset of eyes with an additional criterion of a minimum of four tests was used for trend analyses (P-Trend) (30 healthy controls and 73 patients). For P-Event analysis, test-retest variability thresholds (lower 5th percentile) were estimated with repeat tests within a 4-month period. A P-Event eye was considered a "progressor" if the difference between follow-up and baseline tests exceeded the variability thresholds. For the P-Trend analysis, rates of change were calculated based on least-squares regression. Negative rates with significant (P < 0.05) values were considered progressing. For a reference standard, 17 patient eyes were classified as definitely progressing based on clear evidence of structural and corresponding functional progression. Isolated OCT and VF summary metrics were either inadequately sensitive or not too specific. Combinations of OCT-OCT and OCT-VF metrics markedly improved specificity to nearly 100%. A novel combination of OCT metrics (circumpapillary retinal nerve fiber layer and ganglion cell layer) showed high precision, with 13 of the 15 statistical progressors confirmed as true positives. Although relying solely on metrics is not recommended for clinical purposes, in situations requiring very high specificity and precision, combinations of OCT-OCT metrics can be used. All available OCT and VF metrics can miss eyes with progressive glaucomatous damage and/or can falsely identify progression in stable eyes.

12-month outcomes of ab interno excisional goniotomy combined with cataract surgery in primary open-angle glaucoma and normal tension glaucoma

PurposeTo evaluate the efficacy and safety of excisional goniotomy performed with the Kahook Dual Blade (KDB) combined with cataract surgery in patients with pimary open angle glaucoma (POAG) and Normal Tension Glaucoma (NTG) under topical therapy. Further sub-analysis was performed to compare between 90 and 120 degrees goniotomy.MethodsThis was a prospective case series of 69 eyes from 69 adults (age 78 ± 5.9 years; male = 27, female = 42). Indications for surgery included insufficient IOP control with topical medication, glaucomatous damage progression under topical therapy and reduction of medication burden. Complete success was defined as IOP lowering below 21 mmHg without the need for topical medication. For NTG patients, complete success was defined as IOP lowering below 17 mmHg without the need for topical medication.ResultsIOP was significantly lowered from 19.7 ± 4.7 to 15.1 ± 2.7 at 2 months, 15.8 ± 2.3at 6 months and 16.1 ± 3.2 at 12 months (p < 0.05) for POAG and 15.1 ± 2.5 to 14.1 ± 2.4 at 2 months, 14.1 ± 3.1 at 6 months and 13.6 ± 1.8 at 12 months (p > 0.08) for NTG, respectively. Complete success was achieved in 64% of the patients. IOP lowering under 17 mmHg without the need for topical medication was achieved in 60% of the patients at 12 months. In NTG patients (14 eyes) IOP lowering under 17 mmHg without the need for topical medication was achieved in 71%. No significant difference was recorded in terms of IOP lowering at 12 months in-between 90° and 120° of treated trabecular meshwork (p > 0.7). No severe adverse reactions were recorded in this study.ConclusionOne-year results show that KDB combined with cataract surgery is an effective treatment option for glaucoma patients. IOP lowering was successfully achieved in NTG patients with complete success in 70% of the patients. In our study, no significant differences were recorded in-between 90° and 120° of treated trabecular meshwork.

Peripapillary Oxygenation and Retinal Vascular Responsiveness to Flicker Light in Primary Open Angle Glaucoma.

The aim of our study was to evaluate peripapillary oxygenation and its relationship to retinal vascular responsiveness to flicker light in patients with primary open angle glaucoma (POAG). Retinal vessel oxygen saturation was measured in 46 eyes of 34 Caucasian patients with POAG and in 21 eyes of 17 age-matched controls using the oximetry tool of Retinal Vessel Analyser (RVA: IMEDOS Systems UG, Jena, Germany). The mean oxygen saturation of the major arterioles (A-SO2; %) and venules (V-SO2; %), as well as the corresponding arterio–venular difference (A-V SO2; %), were calculated. We also measured retinal vascular responsiveness (RVR) to flicker light by means of RVA. Glaucoma patients were divided in two subgroups according to their median arteriolar and venular vascular responsiveness to flicker light (AFR and VFR). Glaucomatous damage was assessed by optical coherence tomography (Carl Zeiss Meditec, Dublin, CA, USA) and static automated perimetry (Octopus, program G2/standard strategy: Haag-Streit International, Köniz, Switzerland). In addition, we calculated the mean peripapillary oxygen exposure [ppO2E; %/µm] by dividing the mean A-V SO2 with the mean retinal nerve fibre layer (RNFL) thickness. In glaucoma patients, A-SO2 and V-SO2 values were significantly increased, and their difference decreased when compared to controls (p < 0.017; linear mixed-effects model). Grouped with respect to retinal vascular responsiveness to flicker light, subjects with reduced VFR (≤2.9%) had significantly higher ppO2E (0.49 ± 0.08%/µm, respectively, 0.43 ± 0.06%/µm; p = 0.027). Additionally, higher ppO2E in glaucoma patients correlated negatively with the neuroretinal rim area (p < 0.001) and the RNFL thickness (p = 0.017), and positively with the mean defect of the visual field (p = 0.012). Reduced venular vascular responsiveness in our glaucoma patients was associated with increased peripapillary oxygenation exposure. Thus, ganglion cells and their axons in glaucomatous eyes with reduced retinal vascular responsiveness are prone to be more exposed to higher oxidative stress, probably contributing to the further progression of glaucomatous damage.

Эффективность гониоассоциированной транслюминальной трабекулотомии при вторичной глаукоме на фоне силиконовой тампонады витреальной полости

The main goal of glaucoma treatment is to preserve visual functions and quality of life of patients. In recent years, in connection with the development of vitreoretinal surgery, a number of complications has appeared, one of which is ophthalmic hypertension and progressive glaucomatous damage to the optic disc. An analysis was made of the surgical treatment of 12 patients (12 eyes) with secondary glaucoma after vitreoretinal surgery with the removal of SO 1300 according to gonioscopy-assisted transluminal trabeculotomy (GATT) technique in order to evaluate efficacy and safety. Key words: glaucoma; secondary glaucoma; gonioscopy-assisted trabeculotomy; minimally invasive glaucoma surgery; surgical treatment of glaucoma; silicone oil.

Коррекция вторичной глаукомы с применением гониоассоциированной трансиллюминальной трабекулотомии у пациентов после витреоретинальной хирургии

Purpose. To study the efficacy and safety of gonio-associated transluminal trabeculotomy (GATT) in patients who developed secondary glaucoma after vitreoretinal surgery (VRS) see Silicone Oil Removal (SO) 1300. Material and methods. The analysis of surgical treatment of 12 patients (12 eyes) with a history of vitreoretinal intervention with silicone oil (SO) 1300 tamponade, the average age of patients was 53.6 ± 11.8 years, who underwent surgery according to the GATT method, was performed. Results. Before surgery, the mean IOP was 31.0 ± 4.1 mmHg; at the last postoperative visit, the mean IOP was 15.6 ± 4.6 mmHg (p = 0.033 compared to preoperative data). In the postoperative period, IOP values were significantly lower than in the preoperative period. Before surgery, the average number of antiglaucoma drugs used was 4.8 ±0.9; after surgery, the mean value of antiglaucoma drugs used was 1.6 ± 1.4 (p = 0.025 compared to preoperative data). The most common complication was hyphema, it was observed in 4 patients, which accounted for 33.3 %. Hyphema resolved within 1–3 days. In the postoperative period, jumps in IOP, detachment of the Descemet's membrane, detachment of the choroid, corneal edema and iridodialysis were not observed. The success of surgery was achieved in 11 (91.6 %) patients, while complete success without the use of antiglaucoma drops was achieved in 3 (25.0 %) patients (p = 0.024). Conclusion. The main goal of glaucoma treatment is to preserve the visual function and quality of life of patients. In recent years, in connection with the development of vitreoretinal surgery, a number of complications have appeared, one of which is ophthalmohypertension and progressive glaucomatous damage to the optic disc. There is a need for methods of surgical treatment with minimal trauma to the conjunctiva and sclera, for the possibility of future operations. Based on this study, it can be concluded that GATT is a safe and effective method in the treatment of patients with secondary glaucoma after VRS with CM 1300 removed. However, most patients may require antiglaucoma drugs in the postoperative period. Keywords: glaucoma, secondary glaucoma, gonioassociated trabeculotomy, minimally invasive glaucoma surgery, surgical treatment of glaucoma, silicone oil.

Goldmann Tonometry and Corneal Biomechanics

Glaucoma is the second cause of irreversible blindness in the world. Intraocular pressure (IOP) is a recognized major risk factor for the development and progression of glaucomatous damage. Goldmann applanation tonometry (GAT) is internationally accepted as the gold standard for the measurement of IOP. The purpose of this study was to search for correlations between Goldmann tonometry and corneal mechanical properties and thickness by means of in vitro tests. IOP was measured by the Goldmann applanation tonometer (GIOP), and by a pressure transducer inserted in the anterior chamber of the eye (TIOP), at increasing pressure levels by addition of saline solution in the anterior chamber of enucleated pig eyes (n = 49). Mechanical properties were also determined by inflation tests. The GAT underestimated the real measurements made by the pressure transducer, with most common differences in the range 15–28 mmHg. The difference between the two instruments, highlighted by the Bland–Altman test, was confirmed by ANOVA, normality tests, and Mann–Whitney’s tests, both on the data arranged for infusions and for the data organized by pressure ranges. Pearson correlation tests revealed a negative correlation between (TIOP-GIOP) and both corneal stiffness and corneal thickness. In conclusion, data obtained showed a discrepancy between GIOP and TIOP more evident for softer and thinner corneas, that is very important for glaucoma detection.

A novel rat model of ocular hypertension by a single intracameral injection of cross-linked hyaluronic acid hydrogel (Healaflow® ).

To create a novel animal model of ocular hypertension via the intracameral injection of Healaflow. Unilateral chronic ocular hypertension model of rats was created by the intracameral injection of 3μL Healaflow. The IOP of subjects was monitored. Dynamic morphological changes were evaluated by fundus imaging, OCT and histological examination. Visual function changes were measured by electroretinography and flash visual-evoked potentials. 24 and 72hours after injection, the retinal tissue was collected for transcriptome analysis. The expression levels of related genes and proteins were further evaluated by qRT-PCR and Western blotting. The IOP peaked within 1day after a single intracameral injection of Healaflow and then decreased gradually within 4weeks. Furthermore, the persistently degenerating retinal ganglion cells occurred within 4weeks. The visual function of these rats was also impaired. The results of transcriptome analyses, qRT-PCR and Western blotting showed that the expression levels of B2m, Ikzf1 and Stat3 were up-regulated, while the expression levels of Six3 and Prss56 were down-regulated in the retinal tissues. Intracameral injection of Healaflow is an effective approach to induce glaucomatous neurodegeneration in rats. Six3 and Prss56 may be involved in the pathogenesis of progressive glaucomatous damage.

Pulse Waveform Analysis of the Ocular Blood Flow Using Laser Speckle Flowgraphy before and after Glaucoma Treatment.

Although reduction in intraocular pressure (IOP) is the principle of glaucoma treatment, impaired ocular blood flow is believed to play a role in the progression of glaucoma. This study evaluated the effect of glaucoma treatment on pulse waveforms for optic nerve head (ONH) microcirculation in patients with glaucoma. Fifty-one subjects were included on the basis of the glaucoma treatment administered, which involved instillation of prostaglandin (PG) analogs (PG group; n = 28) or trabeculectomy (trabeculectomy group; n = 23). ONH blood flow, represented by the mean blur rate (MBRT) and pulse waveforms, was measured using laser speckle flowgraphy before and 1 and 3 months after treatment. Three months after treatment, IOP exhibited a significant decrease (p < 0.05). Although there was no significant change in MBRT after treatment, the acceleration time index (ATI) significantly decreased (p=0.034) in the PG group. In the trabeculectomy group, there was no significant change in the MBRT after treatment, while fluctuation (p=0.019) and blowout score (BOS) (p=0.036) exhibited significant decrease and increase, respectively. Multiple regression analysis showed that mean deviation was significantly associated with the rate of change in the BOS (p=0.013), age was a significant contributing factor for the rate of change in fluctuation in the trabeculectomy group, reflection was significantly associated with the ATI (p=0.037) in the in the PG group. Both glaucoma treatments can change the pulse waveforms, with MBRT remaining unchanged, and IOP reduction owing to the treatment may contribute to stable blood flow in the tissue area of the ONH. As impaired ocular blood flow plays a role in the progression of glaucomatous damage, it would be beneficial if glaucoma treatment could improve the stability of ONH microcirculation.

Early diagnostic parameters of glaucoma in high myopes

The goal of this study was to assess changes in OCT parameters occurring in high myopic glaucoma patients, so as to enable early diagnosis and prevention of progressive glaucomatous damage. It was performed at the department of ophthalmology, Kasr Alainy Hospital, Cairo University, over a twenty-month period. This study was a cross-sectional randomized single blinded study. It included 62 eyes of highly myopic individuals. Patients were divided into 2 groups: Group A included myopic non-glaucomatous individuals, and Group B included the myopic glaucoma patients. All patients had a full ophthalmological examination, as well as OCT assessment of the RNFL, GCC and ONH parameters. The VF was tested as well as AXL and CCT. Correlation of the data was performed. Regarding the GLV, its mean in group A was 11.88±6.71% versus 19.69±9.69% in group B; the difference between both groups was statistically significant (P=0.001). Regarding the cup area, the mean in group A was 0.51±0.41mm2, while that in group B was 1.25±0.72mm2; the difference between both groups was statistically significant (P<0.001). The ONH parameter, cup area, and the GCC parameter, GLV, are key parameters in supporting the diagnosis of glaucoma in myopic patients. Other parameters measured by OCT, such as inferior RNFL thickness, FLV, and C/D ratio, could aid in diagnosis as well.

Cytomegalovirus-related uncontrolled glaucoma in an immunocompetent patient: a case report and systematic review

BackgroundCytomegalovirus can cause ocular anterior uveitis with ocular hypertension. Basis on the therapy, ocular pressure usually can be controlled. We report a case of a man who had unilateral cytomegalovirus anterior uveitis with refractory glaucoma during the process of treatment.Case presentationA 57-year-old man who was diagnosed Posner–Schlossman syndrome and was admitted for repeatly attacks of raised IOP in left eye for 4 months. We found the cytomegalovirus -DNA was high (1800 copies/ml) in his aqueous. After systemic used of antiviral drug accompany with topical used of anti-inflammation, anti-glaucoma agents and genciclovir gel, the ocular pressure was dropped to normal. While the pressure elevated again in a month after stopping systemic antiviral treatment. Furthermore, the second test showed cytomegalovirus in aqueous humor decreased to 526 copies/ml. Intravenous drugs to antiviral, anti-inflammatory and anti-glaucoma were applied, but the ocular pressure was still high. In the progression of glaucomatous damage in the eye, glaucoma surgery was operated with no cytomegalovirus was detected. At last, the postoperative ocular pressure has been controlled.ConclusionsCMV infection is not rare. Patients have unilateral mild anterior inflammation with relapsed attacks of elevated intraocular pressure should be considered for CMV infection. We found that concurrent use of systemic and topical ganciclovir in a short period could reduce ocular CMV significantly, while ocular hypertension recurred. The antiviral treatment should be individualized. Glaucoma surgery could be offered to protect CEC loss and glaucomatous damage.

Evaluation of a Region-of-Interest Approach for Detecting Progressive Glaucomatous Macular Damage on Optical Coherence Tomography.

PurposeTo evaluate a manual region-of-interest (ROI) approach for detecting progressive macular ganglion cell complex (GCC) changes on optical coherence tomography (OCT) imaging.MethodsOne hundred forty-six eyes with a clinical diagnosis of glaucoma or suspected glaucoma with macular OCT scans obtained at least 1 year apart were evaluated. Changes in the GCC thickness were identified using a manual ROI approach (ROIM), whereby region(s) of observed or suspected glaucomatous damage were manually identified when using key features from the macular OCT scan on the second visit. Progression was also evaluated using the global GCC thickness and an automatic ROI approach (ROIA), where contiguous region(s) that fell below the 1% lower normative limit and exceeded 288 μm2 in size were evaluated. Longitudinal signal-to-noise ratios (SNRs) were calculated for progressive changes detected by each of these methods using individualized estimates of test–retest variability and age-related changes, obtained from 303 glaucoma and 394 healthy eyes, respectively.ResultsOn average, the longitudinal SNR for the global thickness, ROIA and ROIM methods were −0.90 y−1, −0.91 y−1, and −1.03 y−1, respectively, and was significantly more negative for the ROIM compared with the global thickness (P = 0.003) and ROIA methods (P = 0.021).ConclusionsProgressive glaucomatous macular GCC changes were optimally detected with a manual ROI approach.Translational RelevanceThese findings suggests that an approach based on a qualitative evaluation of OCT imaging information and consideration of known patterns of damage can improve the detection of progressive glaucomatous macular damage.

Glaucoma domiciliary service by optometrist.

Approximately 10% of UK blindness registrations are attributed to glaucoma[1]. The risk of glaucoma increases with age and it is estimated that the prevalence of chronic open angle glaucoma (COAG) is about 10% in white Europeans who are older than 70. There are an estimated 24.4 million people aged over 40 in England and around 489 000 people are currently affected by COAG. These numbers are likely to increase with increasing life expectancy[1]. With aging, there is an increase in prevalence of chronic diseases such as dementia, Alzheimer's disease and osteoarthritis, leading to severe frailty, disability and dependence for their basic needs and care[2]–[3]. The demographic profile of the South West of England shows it one third of it is population living in rural areas (31.3%) which is highest among all English regions. Also, the region's population is oldest with 4.4% people aged over 75, of whom 33% are older than 90. The life expectancy of men and women is also amongst the highest of all counties in the United Kingdom[4]. People diagnosed with COAG are managed by the hospital eye service and lifelong follow-up is normally needed so that any progression of glaucomatous damage can be detected and managed. Sight loss due to glaucoma cannot be restored, and therefore controlling the condition carefully is crucial to maintaining sight. People with severe physical and/or mental disability often reside in care homes and find journeys to hospital stressful, and in many cases not possible, even if appropriate transportation is available. Provisions of community hospitals and mobile clinic reviews has reduced the need to travel to main hospitals, however some patients are still not able to attend. To overcome this problem, a new care pathway called the glaucoma domiciliary service (GDS), managed by optometrists, a central coordinator and consultant glaucoma ophthalmologists was designed and commissioned at the Royal Devon and Exeter (RD&E) Foundation Trust. Glaucoma patients who are unable to attend normal follow-up clinics due to significant physical and/or mental disabilities are offered GDS at their residence. We present the service framework and outcome of our experience of GDS.

Evaluation of Central and Peripheral Visual Field Concordance in Glaucoma.

PurposeThe purpose of this study was to characterize the extent to which central visual field (VF) loss reflects peripheral VF loss in patients with varying degrees of glaucoma severity.MethodsA total of 232 patients with glaucoma or suspect glaucoma completed static central VF testing using the 24-2 pattern and peripheral VF testing using the suprathreshold 30-60 pattern. Points from 24-2 tests were reclassified as normal/abnormal based on pattern deviation values.ResultsStrong positive correlations (r ≥ 0.7) were observed between the proportion of abnormal central and peripheral points for the full VF, superior hemifield, and inferior hemifield, although the percentage of total central and peripheral abnormal points differed by ≥10% in 45% of eyes. In eyes with an average of 10%–40% abnormal points in the central and peripheral VFs, 12.0% more abnormal peripheral points were noted compared with the percentage of abnormal central points (P < 0.001; SD, 16.7%; range, 61% more to 37% less). In eyes with an average of 60%–90% abnormal points in the central and peripheral VFs, 16.4% fewer abnormal peripheral points were noted compared with the percentage of abnormal central points (P = 0.04; SD, 20.9%; range, 19% more to 49% less).ConclusionsCentral 24-2 testing generally reflects the extent of damage to the more peripheral VF in glaucoma, although significant disagreement exists for individual eyes. Further work is needed to determine whether integration of peripheral test points can improve detection of true VF loss in early glaucoma or be useful in monitoring progressive glaucomatous damage to areas of preserved VF in advanced glaucoma.

Glaucoma management after vitreoretinal surgeries.

The surgical management of retinal disorders, including scleral buckling procedures, pars plana vitrectomy, and intravitreal injections of gas or silicone oil, can lead to short-term elevations in intraocular pressure (IOP) and ultimately long-term glaucomatous damage if not treated in a timely manner. Glaucoma in these cases is commonly refractory to conventional therapies. This review highlights the treatment strategies for glaucoma in eyes that have previously undergone vitreoretinal surgery. Although medical therapy is often used initially to control a temporary rise in IOP, laser and surgical therapy may be required to treat sustained IOP elevation and subsequent glaucomatous damage in eyes that have undergone intraocular surgery for retinal disorders. Glaucoma drainage devices are an important treatment modality, particularly when there is high risk of failure with filtering surgery. Previous vitreoretinal surgery is a known risk factor for the development of glaucoma. Treatment is usually initiated with medical therapy, however, surgical intervention is frequently required to control IOP and prevent progressive glaucomatous damage in patients with refractory glaucoma.

Rates of Retinal Nerve Fiber Layer Loss in Contralateral Eyes of Glaucoma Patients with Unilateral Progression by Conventional Methods

To determine whether progressive retinal nerve fiber layer (RNFL) loss occurs in the contralateral eye of patients with glaucoma showing unilateral progression according to conventional diagnostic methods. Prospective, longitudinal, observational cohort study. Three hundred forty-six eyes of 173 patients (118 eyes with glaucoma and 228 eyes with suspect glaucoma at baseline) followed up for an average of 3.5±0.7 years. All subjects underwent standard automated perimetry (SAP; Humphrey Field Analyzer; Carl Zeiss Meditec, Dublin, CA) and spectral-domain (SD) optical coherence tomography (OCT; Spectralis; Heidelberg Engineering, Inc., Carlsbad, CA) in both eyes at 6-month intervals. Eyes were determined as progressing by conventional methods if there was progression on masked grading of optic disc stereophotographs or SAP Guided Progression Analysis (GPA; Carl Zeiss Meditec; "likely progression"). Rates of change in SD OCT average RNFL thickness were obtained using a linear mixed effects model. Rate of global loss was calculated using a random coefficient model and compared for nonprogressing patients, progressing eyes, and fellow eyes of unilateral progressing patients. Rate of change in global RNFL thickness. Thirty-nine subjects showed evidence of unilateral progression by GPA, disc photographs, or both during follow-up. Mean ± standard error rate of RNFL loss in eyes progressing by conventional methods was -0.89±0.22 μm/year (P<0.001). The contralateral eyes of these subjects also showed significant loss of RNFL over time (-1.00±0.20 μm/year; P<0.001). One hundred thirty-four subjects did not show progression by conventional methods in either eye. These eyes also showed a significant decline over time in average RNFL thickness (-0.71±0.09 μm/year; P<0.001); however, the rate of change in these eyes was slower than that of the contralateral eye of patients showing unilateral progression (P<0.001). Loss of RNFL thickness was seen in a substantial number of contralateral eyes of glaucoma patients showing unilateral progression by conventional methods. These findings indicate that assessment of RNFL thickness by SD OCT may show progressive glaucomatous damage that is not detected by visual fields or optic disc stereophotography.

Functional disorders in the chronological progression of glaucoma

Glaucomatous optic neuropathy is a complex process, which not only leads to destruction of the retinal ganglion cells but also negatively influences the third and fourth neurons. Therefore, in histological studies of glaucoma a significant cell loss in both the lateral geniculate nucleus and in the visual cortex could be detected. The involvement of the entire visual pathway in glaucoma leads to a variety of functional disturbances, which are presented in this overview. Besides the well-known visual field defects in glaucomatous optic neuropathy, additional disturbances occur in contrast sensitivity, color vision, stereo vision and increased sensitivity to glare. As a result, faces are less easily recognized , the reading speed is reduced, the location of objects is more complicated and the reaction rate decreases. All these alterations are increased with the progression of glaucomatous damage. The consequences of these visual impairments lead to an increasing social isolation and to an increased risk of falls and driving accidents, thereby significantly reducing the quality of life of glaucoma patients. Therefore, increasing awareness of these visual difficulties is necessary in the special care of patients with glaucoma and the domestic environment should be transformed accordingly.

Surrogates for ocular perfusion pressure are not perfect‐ authors reply

Dr. Khawaja and his colleagues commented on our recent review article (Costa et al. 2013) dealing with ocular perfusion pressure (OPP), and we are grateful for the opportunity to clarify certain points. They have quite correctly commented here, and before in the published letter, they cite (Khawaja et al. 2013) that there are theoretical problems with using the traditional formula for OPP (or more correctly, a surrogate for OPP) derived from brachial artery pressure (BP) and intraocular pressure (IOP), as well as how multivariate analyses are performed. The hidden assumption when testing the impact of OPP on glaucoma is that an abnormally low OPP due to a high IOP may be equivalent to the same OPP due to a low BP. Of course, that is the hypothesis that many of the studies try to address. Stated differently, investigators are attempting to understand whether BP is relevant to the occurrence, severity or progression of glaucomatous damage, or is everything simply dependent on IOP (Costa et al. 2013). Should a surrogate OPP be studied at all? It is difficult, if not impossible, to measure true ocular OPP directly, and if the problem is to be studied, it becomes necessary to use an estimate and hope that the estimate is not too bad. Should the surrogate OPP be corrected for IOP? Probably not, as OPP is calculated with IOP (along with BP) as one of the variables, and hence, multivariate analysis is ruined by the non-independence of the variables OPP and IOP, as Dr. Khawaja and colleagues explain in detail in their already published letter (Khawaja et al. 2013). The corrected value simply represents BP anyway. However, we still believe that this is an important finding, especially because several researchers tended to assume that the only reason for the positive association between OPP and glaucoma was IOP. When one adjusts for IOP and the association remains significant, it is possible to conclude that not only IOP is affecting the positive association, but BP too also is an important driving factor. On the other hand, such analysis does not answer the question of whether OPP itself, whether altered by IOP or BP, is in the final common pathway for damage. It may answer whether BP is relevant, but maybe not whether it is as important the IOP considered by itself. The reviewed studies are not consistent in showing or failing to show a relationship of BP and glaucomatous damage. It does seem that either a very low BP or chronic hypertension, perhaps on treatment with a now-normal BP, each might logically affect the course of glaucoma (Costa et al. 2009). It might be speculated that a sufficiently low BP might indeed result in reduced perfusion. At the same time, long-standing hypertension results in narrowed and stiffened arteries and arterioles, which both increases resistance to flow and impairs the regulatory mechanisms for flow. If so, then the relationship of BP to glaucomatous damage is not linear, because either extreme has an adverse effect. The non-linearity confounds any multivariate analysis that assumes linearity between the independent variables being tested for impact on the dependent variable, glaucomatous damage. Finally, flow depends not only on perfusion pressure, but also on resistance in the vascular bed. The resistance to flow is not fixed, even under completely normal circumstances. The resistance is modified by regulatory mechanisms over a range of perfusion pressures, so the OPP by itself may not have an effect except at the extremes when the capacity for regulation has been exceeded. It is a complex physiological system to study adequately. The innate capacity for regulation may vary from one person to another, and it may be altered by disease, such as stiffening of the arteries by chronic hypertension (arteriosclerosis). Therefore, the review did not have a firm conclusion about the place of OPP in the glaucomatous process. Our only conclusion, cautiously stated in the abstract, is summarized in the sentence: ‘We believe that the balance between IOP and BP, influenced by the autoregulatory capacity of the eye, is part of what determines whether an individual will develop optic nerve damage.’ Dr. Khawaja and colleagues have served us well by highlighting what might be lost in our lengthy review, namely, the difficulties in reaching more targeted conclusions from the studies to date, for both mathematical and physiological reasons. We thank them.

Complementary therapy for the treatment of glaucoma: a perspective.

Although neuroprotective strategies and pharmaceutical agents have been initiated in the treatment of numerous disorders of the central and peripheral nervous systems, including trauma, epilepsy, stroke, Huntington disease, amyotrophic lateral sclerosis,and AIDS dementia, none have yet been applied to the treatment of glaucoma. A prospective, placebo-controlled, multi-institutional trial of memantine is underway. One would not expect the treatment modalities that form the bases of nonpharmaceutical, traditional medical systems to be used to lower IOP. Glaucoma was unknown when these medicinal treatments were developed over the centuries. Their primary use is in improving the cardiovascular and immune systems and in what is now called neuro-protection. Rather than single compounds that target a specific receptor and have demarcated side effects in other systems, plant products are a blend of many compounds and, according to those most versed in them, they achieve a balanced therapy, helping in specific symptomatic complexes while reducing side effects through ameliorating effects in other areas. It is not insignificant that, now that the rain forests are rapidly dwindling, together with their inhabitants and the knowledge of medicinal plants (especially in South America), the pharmaceutical companies are spending large amounts of money in a sudden, almost frantic attempt to gather the knowledge about rainforest plants before all has been completely lost. Proof of effects clinically in a chronic disease such as glaucoma remains largely lacking, and controlled trials are unlikely to be initiated, except perhaps through the National Institutes of Health, because these compounds have been in the public domain for many years. Perhaps those as yet unknown or un-recorded are patentable and perhaps these include drugs known only to small surviving communities of hunter-gatherers, which explains the pharmaceutical interest in these areas. When more accurate and rapid means of assessment of progression of glaucomatous damage than perimetry and optic nerve head photography are eventually developed and trials can be reduced in time, number of subjects, or even the use of nonhuman subjects for the bulk of studies, studies could be done for verification of effect of various compounds and also comparative studies. At the present time, GBE is the best documented of all the complementary medicinal agents and seems to have the greatest potential value. Ginkgo biloba extract has numerous properties that theoretically should be beneficial in treating non-IOP-dependent mechanisms in glaucoma. Its multi-ple beneficial actions, including increased ocular blood flow, antioxidant activity, platelet activating factor inhibitory activity, nitric oxide inhibition, and neuroprotective activity, combine to suggest that GBE could prove to be of major therapeutic value in the treatment of glaucoma.

Changes in the retrobulbar hemodynamic parameters after decreasing the elevated intraocular pressure in primary open-angle glaucoma patients.

Ocular blood flow (OBF) disturbances could be involved both in the pathogenesis and in progression of glaucomatous damage. The aim of the study was to compare the retrobulbar hemodynamic parameters in the ophthalmic artery (OA), central retinal artery (CRA) and short posterior cilliary arteries (SPCA) after decreasing the elevated intraocular pressure (IOP) in primary open-angle glaucoma (POAG) patients by using color Doppler imaging (CDI). We examined 60 patients (21 male and 39 female) with diagnosed and treated POAG. Thirty-nine patients had increased IOP (> 25 mm Hg). Peak-systolic velocity (PSV), end-diastolic velocity (EDV), Pourcelot resistance index (RI), and pulsatility index (PI) were assessed in the OA, CRA, and SPCA. IOP was measured both with the Goldmann Applanation tonometer (GAT) and with the Dynamic Contour tonometer (DCT), three times respectively. Ocular pulse amplitude (OPA) was measured using DCT. The retrobulbar parameters between the baseline and after IOP reduction showed no difference in measurements. After Bonferroni correction (p < or = 0.0056, alpha/9) statistical significance was recorded only in the following retrobulbar hemodynamic parameters; DCT (29.8 +/- 6.2 vs. 15.5 +/- 5.0), GAT (33.8 +/- 9.0 vs. 15.0 +/- 6.6) and OPA measurements (4.3 +/- 1.0 vs. 3.0 +/- 1.6), as compared to the baseline. There was no correlation between the changes in IOP measured with either DCT or GAT and changes in the hemodynamic parameters (p > 0.05 for all). Pearson correlation coefficient (95% CI) showed very good correlation for IOP measurements between DCT and GAT: at baseline 0.83 (0.71 to 0.90) and at the end 0.71 (0.55 to 0.83); p < 0.0001 for both measurements, but without any difference between them (p > 0.05). There was a lack of correlation between the changes in IOP measured with either DCT or GAT and the changes in the hemodynamic parameters.

Imaging of the optic nerve and retinal nerve fiber layer: An essential part of glaucoma diagnosis and monitoring

Because glaucomatous damage is irreversible early detection of structural changes in the optic nerve head and retinal nerve fiber layer is imperative for timely diagnosis of glaucoma and monitoring of its progression. Significant improvements in ocular imaging have been made in recent years. Imaging techniques such as optical coherence tomography, scanning laser polarimetry and confocal scanning laser ophthalmoscopy rely on different properties of light to provide objective structural assessment of the optic nerve head, retinal nerve fiber layer and macula. In this review, we discuss the capabilities of these imaging modalities pertinent for diagnosis of glaucoma and detection of progressive glaucomatous damage and provide a review of the current knowledge on the clinical performance of these technologies.