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Excerpts from:

Volume 14-4 2013


The Cost of Glaucoma Care (2002-2009)
Long-term postoperative complications in patients randomized to trabeculectomy in the Collaborative Initial Glaucoma Treatment Study (CIGTS): The risk of blebitis and hypotony was each 1.5% at five years and the risk of endophthalmitis was 1.1% at five years.

In 2009, office visits comprised nearly one-half of glaucoma-related costs, diagnostic testing was about one-third, and surgical and laser procedures were about 10% of costs each. From 2002 to 2009, glaucoma care costs per person per year rose from $197 to $228, less than 1/200th of all Medicare payments, and increasing at less than the rate of general or medical inflation.

Large and Sustained Blood Pressure Dips Are Associated With Visual Field Progression and Normal-Tension Glaucoma.
This suggests that 24-hour BP monitoring may be useful in NTG patients.


M & T: At the European Society Meeting (June 2014), it was recommended to order a 24-hour blood pressure monitoring for patients with "normal-tension glaucoma" who continue to progress in spite of perceived adequate IOP control. This is most certainly something to be considered when faced with such patients.

A Prospective Randomized, Multicenter, Single-Masked, Parallel, Dose Ranging Study To Compare the Safety and Efficacy of BOL-303259-X to Latanoprost in Subjects with Open-Angle Glaucoma or Ocular Hypertension
BOL-303259-X is a nitric oxide donating prostaglandin F2a agonist. Following randomization, 413 eligible subjects with a diagnosis of open-angle glaucoma or ocular hypertension were assigned to one of five treatment groups: BOL-303259-X 0.006%, 0.012%, 0.024%, 0.040%, or latanoprost 0.005% ophthalmologic solutions. After 28 days of once-daily treatment, mean diurnal IOP reduction in the BOL-303259-X 0.024% (9mmHg; p= 0.0051) and 0.040% (8.9mmHg; p=0.0089) treatment groups was greater than the latanoprost group (7.8mmHg); on Day 29, a greater mean diurnal IOP reduction was still observed in the BOL-303259-X 0.024% group (7.20 versus 6.25mmHg; p= 0.0056) compared to latanoprost. Conjunctival hyperemia was similar across all treatment options. These results indicate that BOL-303259-X is a safe and effective IOP-lowering agent with greater IOP reduction than latanoprost with the 0.024% concentration, while retaining a similar side effect profile.

Cataract Surgery to Lower IOP
Recent clinical trials have confirmed earlier reports that modern cataract surgery with phacoemulsification should be considered an intraocular pressure (IOP) lowering procedure. The degree of average IOP lowering is positively related to the level of IOP with greater expected reduction in those with the highest baseline IOP.

Multifocal IOLs and Glaucoma
It is becoming known that contrast sensitivity is reduced in patients with glaucoma, even those with minimal visual field defects. Diffractive optics multifocal IOLs trade contrast for two simultaneous images. For patients with glaucoma, taking a hit in contrast sensitivity from two different directions may make the long-term placement of a diffractive optics multifocal IOL problematic, with gradually increasing visual disability.

Establishing Baseline Visual Fields
When establishing a baseline set of visual fields, obtain two and separate them by less than one month. Generally, if you explain to the patient that this is the baseline that they are going to have to compare against for many years, they will endorse the plan.

Glaucoma Risk Factors Versus Glaucoma Manifestation
The risk factors for glaucoma and glaucoma manifestation have to be discriminated. Risk factors are detectable via medical history of the patient or objective examination (high IOP, thin cornea, gonioscopy). Not even the presence of all of these risk factors is enough for glaucoma diagnosis, the risk factors only enhance it probability.


M & T: Glaucoma is definitively diagnosed with a repeatable visual field defect.


More on Cataract Surgery to Lower IOP
Modern cataract surgery using phacoemulsification is undoubtedly the most commonly performed IOP-lowering procedure worldwide today. Although a small risk for complications exists, it is hard to argue against the fact that the benefits of early cataract surgery outweigh the risks in most patients with mild, moderate, and, in some cases, advanced glaucomatous disease.


Glaucoma Opinion: Prostaglandin-Associated Periorbitopathy (PAP): Clinical Features. Pathophysiology and implications
We have performed a comprehensive search using PubMed to identify all reported cases of Prostaglandin-Associated Periorbitopathy (PAP). Ten articles were found in English literature dating back to 2004, reporting 39 cases of PAP; 23 cases resulting from bimatoprost use, eight cases from travoprost use and eight cases from latanoprost.


Clinical Features
The following clinical features of PAP have been described:

  • Upper lid ptosis

  • Deepening of upper lid sulcus

  • Involution of dermatochalasis

  • Orbital fat atrophy​

  • Mild enophthalmos

  • Inferior scleral show

  • Reduction of the interior eyelid bags

  • Tight orbits


These effects arise after a period of several weeks to several years on treatment with PGAs.
Most of the anatomical changes of PAP are thought to be due to orbital fat atrophy, while dehiscence of the levator aponeurosis or Muller's muscle may account for the upper lid ptosis.


The mechanism of the fat atrophy appears to be related to the effect of the prostaglandin F2alpha (PGF2 alpha) on adipocytes. Studies have shown that PGF2 alpha inhibits adipogenesis by activating mitogen-activated protein kinase.

In vitro studies comparing the different PGAs showed that bimatoprost had the most anti-adipogenic effect and latanoprost had the least.

The mechanism for blepharoptosis is less clear, immunohistochemistry studies have shown a decrease in collagen types I, III, and IV in the ciliary body of monkey eyes treated with PGAF2 alpha compared with untreated eyes. It is possible that PGAs could also decrease the amount or weaken the structure of collagen in the levator aponeurosis or Muller's muscle ligament, resulting in ptosis.

Potency of Onset PAP
Many authors have reported reversal of PAP after discontinuation of bimatoprost and travoprost. Reversal of upper eyelid sulcus deepening has been reported to occur anywhere from four weeks to nine months after cessation of bimatoprost therapy. The signs of travoprost-induced PAP have been reported to resolve anywhere between two and 15 months after discontinuation of travoprost. Of the two existing articles reporting latanoprost-induced PAP, the medication was not discontinued, so reversal could not be noted. It is possible that some cases of PAP after long-term use may not be reversible.


Clinical Implications of PAP
The anatomic changes to the periorbital soft tissues should not be taken lightly. It can be cosmetically unappealing and especially noticeable in monocularly treated patients. Asymmetry of the orbits and eyelids has led to unnecessary imaging and workup for causes of unilateral enophthalmos or apparent contralateral proptosis.
The deep orbits and tight eyelids present a challenge to eyecare clinicians when examining the eye and performing procedures. Goldmann applanation tonometry, for instance, is more difficult to perform as both the patient and the clinician have difficulty lifting up the patient's ptotic upper eyelid.


Factors Affecting IOP
In the supine position, IOP was significantly higher in the eye with the more advanced visual field loss. In the lateral decubitus position, the IOP was higher than in the supine position, and the IOP of the dependent (lower) eye was higher than the nondependent eye. Interestingly, the IOP difference between the two eyes was greater when the eye with the more advanced visual field loss was in the dependent position that in the non-dependent position. These results suggest that eyes with more advanced glaucoma have a different IOP response to changes in body position than eyes with milder disease. However, the significance of these findings to clinical management is not clear at this time. It is possible that greater IOP rise in the supine and lateral decubitus position is what predisposes to more advanced disease. It is also possible that these IOP changes are incidental findings, and other factors, such as pressure on the dependent eye by the pillow in the lateral decubitus position, are the true causes.


IOP Instruments in Children
The iCare rebound tonometer has proven invaluable in the assessment of children with known or suspected glaucoma. Although the device often reports IOP to be slightly higher than measured with Goldmann applanation tonometry in cooperative children, its low rate of 'false low' IOP readings makes it an almost ideal screening tool for the pediatric population requiring IOP measurement.
The results of this study support the general impression that iCare rebound tonometry makes IOP assessment in non-sedated children much easier, and that real benefit ensues, in terms of anesthetic sessions saved and even cost incurred for care of pediatric glaucoma patients.


Prostaglandin Side Effects
Prostaglandin-associated periorbitopathy (PAP) has recently gained attention. PAP results from atrophy of periorbital adipocytes, and consists of ptosis, deepening of the upper eyelid sulcus (DUES), involution of dermatochalasis, loss of the inferior orbital fat pads, enophthalmos, inferior scleral show, and tight orbits. The authors found in a former study that switching 25 Japanese patient with OAG being treated in both eyes with latanoprost for more than 12 months to bimatoprost resulted in 15 patients (60%) developing DUES within six months. In the present study, the authors switched 13 of these 15 patients back to latanoprost, and found in 11 of the 13 (85%), DUES had either decreased or disappeared within two months. Further research needs to be done to determine the frequency of PAP, how long it takes to occur, how long it takes to resolve after discontinuation of PGAs, and any differences that may exist based on age, race, and type of PGA used.


Eyedrop Formulation
Glaucoma topical therapeutics preserved with BAK have been used chronically by patients for decades and appear to be safe and well-tolerated in the overwhelming majority of those treated. It is possible that the physiologic effect on the eye is not substantial enough to induce measurable damage and/or that the eye can overcome such effects by inherent compensatory mechanisms such as anti-oxidant reserves. Alternatively, the very treatment being prescribed to patients may lead to damage that could potentially worsen disease.

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