John P. Berdahl

Cerebrospinal fluid pressure is decreased in primary open-angle glaucoma.

PURPOSE To compare cerebrospinal fluid (CSF) pressure in patients with primary open-angle glaucoma (POAG) with that in nonglaucomatous patients. DESIGN Case-control study. PARTICIPANTS Thirty-one thousand, seven hundred and eighty-six subjects underwent lumbar puncture (LP) between 1996 and 2007 at the Mayo Clinic, Rochester, Minnesota. Of these, 28 patients who had POAG and 49 patients who did not have POAG were analyzed. METHODS Retrospective review of medical records. Comparison of the 2 groups and factors associated with CSF pressure were analyzed by univariate and multivariate analyses. MAIN OUTCOME MEASURES Demographics (age and gender), medical history, medication use, indication for LP, intraocular pressure (IOP), optic disc cup-to-disc ratio, visual field assessment, and CSF pressure. RESULTS The mean CSF pressure +/- standard deviation was 13.0+/-4.2 mmHg in nonglaucoma patients and 9.2+/-2.9 mmHg in POAG patients (P<0.00005). The CSF pressure was lower in POAG patients regardless of indication for LP or age. Linear regression analysis showed that cup-to-disc ratio correlated independently with IOP (P<0.0001), CSF pressure (P<0.0001), and the translaminar pressure difference (P<0.0001). Multivariate analysis demonstrated that larger cup-to-disc ratio (P<0.0001) was associated with lower CSF pressure. CONCLUSIONS Cerebrospinal fluid pressure is significantly lower in POAG patients compared with that in nonglaucomatous controls. These data support the notion that CSF pressure may play an important contributory role in the pathogenesis of POAG.

Intracranial Pressure in Primary Open Angle Glaucoma, Normal Tension Glaucoma, and Ocular Hypertension: A Case–Control Study

PURPOSE To compare intracranial pressure (ICP) in subjects with primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG; subset of POAG), and ocular hypertension (OHT) with that in subjects with no glaucoma. METHODS The study was a retrospective review of medical records of 62,468 subjects who had lumbar puncture between 1985 and 2007 at the Mayo Clinic. Of these, 57 POAG subjects, 11 NTG subjects (subset of POAG), 27 OHT subjects, and 105 control subjects met the criteria and were analyzed. A masked comparison of the relationship between ICP and other ocular and nonocular variables was performed by using univariate and multivariate analyses. RESULTS ICP was significantly lower in POAG compared with age-matched control subjects with no glaucoma (9.1 +/- 0.77 mm Hg vs. 11.8 +/- 0.71 mm Hg; P < 0.0001). Subjects with NTG also had reduced ICP compared with the control subjects (8.7 +/- 1.16 mm Hg vs. 11.8 +/- 0.71 mm Hg; P < 0.01). ICP was higher in OHT than in age-matched control subjects (12.6 +/- 0.85 mm Hg vs. 10.6 +/- 0.81 mm Hg; P < 0.05). CONCLUSIONS ICP is lower in POAG and NTG and elevated in OHT. ICP may play an important role in the development of POAG and NTG and in preventing the progression of OHT to POAG. Further prospective and experimental studies are warranted to determine whether ICP has a fundamental role in the pathogenesis of glaucoma.

Corneal wound architecture and integrity after phacoemulsification: Evaluation of coaxial, microincision coaxial, and microincision bimanual techniques

PURPOSE: To compare the effects of microincision bimanual phacoemulsification, standard coaxial phacoemulsification, and microincision coaxial phacoemulsification on clear corneal incision architecture and wound integrity. SETTING: Department of Ophthalmology, Duke University, Durham, North Carolina, USA. METHODS: A prospective study of 15 human cadaver eyes (3 groups of 5 eyes) ranging 1 to 4 days postmortem had simulated phacoemulsification by bimanual phacoemulsification (1.2 mm incision), standard coaxial phacoemulsification (2.75 mm), or microincision coaxial phacoemulsification (2.2 mm). All phacoemulsification settings were kept constant across each group. After phacoemulsification, intraocular pressure (IOP) was cyclically raised and lowered from 0 to 125 mm Hg. Two eyes in each group had India ink placed above the wound, and the IOP was varied as above. Entry of India ink into the wound or aqueous leakage from the wound was recorded. The same 2 corneas in each group were removed for histopathologic review of India ink penetration. Scanning electron microscopy was used to evaluate wound architecture in 1 eye in each group. RESULTS: Spontaneous wound leakage was evident in all 5 eyes having bimanual phacoemulsification, in 1 eye (20%) having standard coaxial phacoemulsification, and no eye having microincision coaxial phacoemulsification. India ink penetration was grossly evident in 2 of 2 eyes having bimanual phacoemulsification, 1 of 2 eyes having standard coaxial phacoemulsification, and neither of the 2 eyes having microincision coaxial phacoemulsification. Scanning electron microscopy showed increased endothelial cell loss and greater compromise to Descemets membrane with bimanual phacoemulsification than with standard coaxial phacoemulsification or microincision coaxial phacoemulsification. CONCLUSION: Results in this experimental setting suggest microincision coaxial phacoemulsification and standard coaxial phacoemulsification induce less wound stress and alteration of wound morphology leading to wound leakage than microincision bimanual phacoemulsification.

Intracranial pressure and glaucoma.

Purpose of review Glaucoma remains a disease with an unclear basic pathophysiology. The optic nerve travels through two pressurized regions: the intraocular space and the intracranial space. Some authors have suggested that the relationship between intraocular pressure and intracranial pressure may play a fundamental role in the development of glaucoma. Recent findings Recent studies have shown that intracranial pressure is lower in patients with glaucoma and normal-tension glaucoma. Conversely, intracranial pressure appears to be elevated in patients with ocular hypertension. Early mathematical modeling studies have suggested that the counterbalance provided by intracranial pressure would be an important factor in the development of glaucoma. Summary The relationship between intraocular pressure and intracranial pressure may play an important role in the development of glaucoma.

Body mass index has a linear relationship with cerebrospinal fluid pressure.

PURPOSE To examine the relationship between body mass index (BMI) and cerebrospinal fluid pressure (CSFP), as low BMI and low CSFP have recently been described as risk factors for primary open-angle glaucoma (POAG). METHODS This was a retrospective review of the electronic medical records of patients who had CSFP measured by lumbar puncture and data to calculate BMI at the Mayo Clinic (Rochester, MN). Exclusion criteria included diagnoses, surgical procedures and medications known to affect CSFP. Mean CSFP for each unit BMI was calculated. The probabilities were two-tailed, and the α level was set at P < 0.05. Patients with documented BMI, CSFP, and intraocular pressure (IOP) were analyzed for the relationship between IOP and BMI. RESULTS A total of 4235 patients, primarily of Caucasian descent, met the entry criteria. Median BMI was 26 and the mean CSFP was 10.9 ± 2.6 mm Hg. The increase in CSFP with increasing BMI was linear with an r(2) = 0.20 (P < 0.001). CSFP increased by 37.7% from BMI 18 (8.6 ± 2.1 mm Hg) to BMI 39 (14.1 ± 2.5 mm Hg). The r(2) (0.21) of the model of BMI and sex was similar to the r(2) of a BMI-only model (0.20). There was no relation between IOP and BMI within a subgroup of the study population (r (2) = 0.005; P = 0.14). CONCLUSIONS CSFP has a positive, linear relationship with BMI. IOP is not influenced by BMI. If CSFP influences the risk for POAG, then individuals with a lower BMI may have an increased risk for developing POAG. Similarly, a higher BMI may be protective.

Cerebrospinal Fluid Pressure Decreases with Older Age

Purpose Clinical studies implicate low cerebrospinal fluid pressure (CSFP) or a high translaminar pressure difference in the pathogenesis of primary open angle glaucoma (POAG) and normal tension glaucoma (NTG). This study was performed to examine the effect of age, sex, race and body mass index (BMI) on CSFP. Methods Electronic medical records from all patients who had a lumbar puncture (LP) performed at the Mayo Clinic from 1996–2009 were reviewed. Information including age, sex, race, height and weight, ocular and medical diagnoses, intraocular pressure (IOP) and LP opening pressure was obtained. Patients using medications or with medical diagnoses known to affect CSFP, and those who underwent neurosurgical procedures or where more than one LP was performed were excluded from analysis. Results Electronic medical records of 33,922 patients with a history of having an LP during a 13-year period (1996–2009) were extracted. Of these, 12,118 patients met all entry criteria. Relative to mean CSFP at age group 20–49 (mean 11.5±2.8 mmHg), mean CSFP declined steadily after age 50, with percent reduction of 2.5% for the 50–54 age group (mean 11.2±2.7 mmHg, p<0.002) to 26.9% for the 90–95 group (mean 8.4±2.4 mmHg, p<0.001). Females had lower CSFP than males throughout all age groups. BMI was positively and independently associated with CSFP within all age groups. Conclusion There is a sustained and significant reduction of CSFP with age that begins in the 6th decade. CSFP is consistently lower in females. BMI is positively and independently associated with CSFP in all age groups. The age where CSFP begins to decline coincides with the age where the prevalence of POAG increases. These data support the hypothesis that reduced CSFP may be a risk factor for POAG and may provide an explanation for the mechanism that underlies the age-related increase in the prevalence of POAG and NTG.

Comparison of Sutures and Dendritic Polymer Adhesives for Corneal Laceration Repair in an In Vivo Chicken Model

OBJECTIVE To compare clinical and histologic healing of corneal lacerations repaired by sutures or a new polymeric adhesive. METHODS A central full-thickness 4.1-mm laceration was made in the right eyes of 60 white leghorn chickens. Half of the wounds were treated with biodendrimer polymer adhesive and half were closed with 3 interrupted 10-0 nylon sutures. Slitlamp examination was performed at 6 hours, daily for 7 days, and weekly for 21 days. Animals were humanely killed at days 1, 3, 7, and 28 for histologic examination to evaluate corneal healing. RESULTS Histologic observations on days 1, 3, and 7 showed glued wounds filled with fibrin, then hyperplastic epithelium, and subsequently scar tissue. Scarring was more prominent at day 7 in glued corneas; however, by day 28, sutured corneas exhibited more inflammation and scarring and much more irregular anterior corneal surfaces. Clinically, all glued corneas remained clear while nearly all sutured corneas had some degree of corneal scarring persisting through day 28. The procedure was about 5 times faster with sealant than with sutures. CONCLUSION Corneal lacerations treated with adhesive heal favorably compared with sutures. CLINICAL RELEVANCE Biodendrimer adhesives represent a safe, effective, and technically easier alternative to traditional suture repair of corneal perforations.

The translaminar pressure gradient in sustained zero gravity, idiopathic intracranial hypertension, and glaucoma

Papilledema has long been associated with elevated intracranial pressure. Classically, tumors, idiopathic intracranial hypertension, and obstructive hydrocephalus have led to an increase in intracranial pressure causing optic nerve head edema and observable optic nerve swelling. Recent reports describe astronauts returning from prolonged space flight on the International Space Station with papilledema (Mader et al., 2011) [1]. Papilledema has not been observed in shorter duration space flight. Other recent work has shown that the difference in intraocular pressure (IOP) and cerebrospinal fluid pressure (CSFp) may be very important in the pathogenesis of diseases of the optic nerve, especially glaucoma (Berdahl and Allingham, 2009; Berdahl, Allingham, et al., 2008; Berdahl et al., 2008; Ren et al., 2009; Ren et al., 2011) [2-6]. The difference in IOP and CSFp across the lamina cribrosa is known as the translaminar pressure difference (TLPD). We hypothesize that in zero gravity, CSF no longer pools in the caudal spinal column as it does in the upright position on earth. Instead, CSF diffuses throughout the subarachnoid space resulting in a moderate but persistently elevated cranial CSF pressure, including the region just posterior to the lamina cribrosa known as the optic nerve subarachnoid space (ONSAS). This small but chronically elevated CSFp could lead to papilledema when CSFp is greater than the IOP. If the TLPD is the cause of optic nerve head edema in astronauts subjected to prolonged zero gravity, raising IOP and/or orbital pressure may treat this condition and protect astronauts in future space travels from the effect of zero gravity on the optic nerve head. Additionally, the same TLPD concept may offer a deeper understanding of the pathogenesis and treatment options of idiopathic intracranial hypertension (IIH), glaucoma and other diseases of the optic nerve head.

Dysfunctional tear syndrome: dry eye disease and associated tear film disorders - new strategies for diagnosis and treatment.

Dysfunctional tear syndrome (DTS) is a common and complex condition affecting the ocular surface. The health and normal functioning of the ocular surface is dependent on a stable and sufficient tear film. Clinician awareness of conditions affecting the ocular surface has increased in recent years because of expanded research and the publication of diagnosis and treatment guidelines pertaining to disorders resulting in DTS, including the Delphi panel treatment recommendations for DTS (2006), the International Dry Eye Workshop (DEWS) (2007), the Meibomian Gland Dysfunction (MGD) Workshop (2011), and the updated Preferred Practice Pattern guidelines from the American Academy of Ophthalmology pertaining to dry eye and blepharitis (2013). Since the publication of the existing guidelines, new diagnostic techniques and treatment options that provide an opportunity for better management of patients have become available. Clinicians are now able to access a wealth of information that can help them obtain a differential diagnosis and treatment approach for patients presenting with DTS. This review provides a practical and directed approach to the diagnosis and treatment of patients with DTS, emphasizing treatment that is tailored to the specific disease subtype as well as the severity of the condition.

Thermal study of longitudinal and torsional ultrasound phacoemulsification: tracking the temperature of the corneal surface, incision, and handpiece.

PURPOSE: To evaluate the change and difference in the corneal surface, incision, and handpiece temperatures during longitudinal and torsional ultrasound (US) phacoemulsification with standard incisions (2.75 mm) and microincisions (2.20 mm) and the thermal effect on wounds. SETTING: Department of Ophthalmology, Duke University, Durham, North Carolina, USA. METHODS: In this prospective study, human cadaver eyes had simulated phacoemulsification. Group 1 had a 2.75 mm incision with 100% longitudinal US; Group 2, a 2.20 mm incision with 100% longitudinal US; Group 3, a 2.75 mm incision with 100% torsional US; and Group 4, a 2.20 mm incision with 100% torsional US. During phacoemulsification, the corneal incision was evaluated by surgical microscopy and scanning electron microscopy (SEM) and images of the corneal surface, incision, and handpiece were captured with an infrared camera. RESULTS: Twelve eyes (3 each group) were evaluated. The maximum incision temperature was higher in the longitudinal groups than in the torsional groups. With the same US modality, the maximum microincision temperature was higher than the maximum standard incision temperature. After application of full power for 40 seconds, wound burn was observed in all eyes in the longitudinal groups and no eyes in the torsional groups. On SEM, there was more extensive loss of Descemet membrane in the longitudinal groups than in the torsional groups. CONCLUSION: Incision temperature was influenced by US modality and was significantly lower with torsional US than with longitudinal US. Using torsional US with smaller incisions may decrease the risk for wound burn in eyes with denser cataracts. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. Additional disclosure is found in the footnotes.