Novel anticoagulants agents may provide lower risk of intraocular hemorrhage


Novel antithrombotic pose an equal or lower risk of intraocular hemorrhage than their traditional counterparts, according to this analysis of insurance claims. 

Study design

This retrospective cohort study analyzed the safety profiles of novel anticoagulants and antiplatelet therapy. Investigators analyzed the incidence of intraocular hemorrhage between months 3 and 12 among new users of antithrombotic drugs.


A statistical comparison of 146,137 patients taking warfarin and 64,291 patients taking novel anticoagulants dabigatran (Pradaxa) or rivaroxaban (Xarelto) revealed a slightly lower risk of hemorrhage in the latter group at 365 days (HR 0.75; P=0.03).

However, a comparison of 103,796 patients taking clopidogrel with 8,386 patients taking novel antiplatelet therapy prasugrel revealed no differences (P=0.53).


The study was unable to determine if patients temporarily stopped their medication at or around the time of eye surgery. Since the rate of intraocular hemorrhages was exceedingly low, the power of the study to detect subtle differences between antiplatelet cohorts was limited despite the large number of patients.

The authors defined intraocular hemorrhage as vitreous hemorrhage, non-traumatic intraocular hemorrhage, hyphema, choroidal hemorrhage, as well as retinal hemorrhage. While choroidal hemorrhage or vitreous hemorrhage and hyphema would be considered significant, retinal hemorrhage may be small and not clinically significant.

Additionally, there are other antithrombotic agents that were not examined in this study. Finally, there is no mention of other intraocular complications during surgery attributable to these drugs.

Clinical significance

There has been an increase in the use of novel anticoagulant and antiplatelet medications due to their ease of use, improved adverse effect profiles, less need for monitoring and superior efficacy. These real-world findings corroborate what has been observed in randomized controlled trials, and support the safety of these novel drugs.

This study suggests that there is not an increased risk of intraocular hemorrhage associated with the use of novel P2Y12 inhibitor Effient compared with Plavix. It also suggests that novel direct thrombin inhibitors and direct factor Xa inhibitors (Pradaxa and Xarelto, respectively) may actually decrease the risk of bleeding compared with traditional vitamin K anticoagulant warfarin.

Blood Vessel Support and Prevention Package for Macular Degeneration Support

amd-4g2-email.gifA major problem with advanced Macular Degeneration is the growth of blood vessels in the eye. These unwanted blood vessels develop in the late stages of Age-Related Macular Degeneration (ARMD), also known as “wet” ARMD. Dr. Marc Grossman at Natural Eye Care has developed a package of supplements aimed at strengthening the retina and reducing the risk of new blood vessel growth.

New blood vessels obscure vision. Wet ARMD patients have few options. Doctors can sometimes zap the eye with lasers in an attempt to reduce the rate of future blood vessel growth. Oral drugs such as ranibizumab can help stop new blood vessels from developing. Injectable drugs are also aimed at stopping the extra blood vessel growth. All these options carry potential side effects and damage.

In consultation with their eye doctors, some wet AMD patients have tried research-based targeted nutrition. Certain vitamins, nutrients, homeopathics, and Traditional Chinese Medicine remedies are aimed at supporting the eyes. The AMD Package 4G2 contains nutrients to help strengthen the retina, and blood vessels, and reduce the risk of new unwanted blood vessel growth.

Contents of the ARMD Package

Advanced Eye and Vision Support Formula provides antioxidants for both eyes and total body health. Eye-specific nutrients include lutein, bilberry, special Chinese herbs, carrot root, and more.

Krill Oil Complex is an important source of omega-3 fatty acids.  Additionally, krill provides a treasured antioxidant for heart and vision health called “astaxanthin.” (LINK)

Vitamin D3 is for retinal and overall body support. Research has indicated this vitamin could reduce ARMD risk.1 Many Americans have low vitamin D due to indoor activities and less sunlight exposure in the winter. Vitamin D supports immunity, skeletal health, the heart, and cognition.

Dr. Grossman’s Blood Vessel Formula is designed to help prevent the growth of unwanted blood vessels. This wild-crafted herbal formula is based on a National Institutes of Health study.2 Includes ginkgo biloba, grape extract, cinnamon, ginseng and more. Click for ingredients.

See the AMD Package 4G2 in the Natural Eye Care Store.

Surgical management strategies for trachomatous trichiasis

This Current Insight outlines current evidence supporting surgical management strategies for trachomatous trichiasis.

PLTR and BLTR: Two tried and tested techniques

Published in the August 2017 issue of Ophthalmology, the study Predictors of Trachomatous Trichiasis Surgery Outcome compares 2 tarsal rotation surgeries: posterior lamellar tarsal rotation (PLTR) and bilamellar tarsal rotation (BLTR).

Clinical trials have shown that PLTR and BLTR are more effective than alternative surgical procedures for the management of trachomatous trichiasis (TT) in trachoma-endemic settings. These tarsal rotation procedures are therefore recommended by the World Health Organization (WHO). 

In particular, two trials examined the relative effectiveness of BLTR, tarsal advance and rotation, eversion splinting, tarsal advance (lid split), tarsal advance and grafting, and tarsal grooving. Both trials found the BLTR procedure to be superior than other strategies for the management of TT.1,2 Furthermore, BLTR can be readily taught to non-ophthalmologists, and can be easily and safely performed in rural health facilities. These are key advantages because, worldwide, most TT surgeries are delivered by non-physician health workers.

ALR: An unknown entity

To date, no randomized controlled trials have compared the anterior lamellar recession/repositioning (ALR) with either BLTR or PLTR for trachomatous trichiasis. One retrospective case series compared outcomes of BLTR and ALR procedures performed at different times. The study found a 46% risk of recurrance for BLTR and 17% risk for ALR, but these did not reach statistical significance.3 However, that study was limited by inconsistent follow-up times, a lack of surgeon standardization and an inadequate sample size, which make it difficult to draw meaningful conclusions.

A prospective noncomparative study conducted in Egypt reported a 34% recurrence rate at 6 months after ALR.4 A prospective non-comparative series from Iran of 32 cases with upper lid cicatricial entropion found a 25% recurrance rate at 1 year for ALR combined with blepharoplasty (excision of excess anterior lamella) and supratarsal fixation.5 These recurrence rates are higher than those reported in a recent trial comparing PLTR and BLTR (13% and 22%, respectively, at 1 year).6

In the aforementioned studies of ALR for TT, surgery was conducted by highly experienced surgeons; recurrence rates may be higher when performed by non-physician cadres with relatively limited training.7,8  Previous studies have consistently found that surgeon technique/ability is a crucial determinant of success.

Drawbacks of ALR

Critics have noted that ALR may not be sufficient for some phenotypes of TT because it does not address the posterior lamella. Therefore, it may prove ineffective in cases with severe posterior lamellar scarring and shortening, or cases with metaplastic lashes emanating from the posterior lamella, which occur commonly in trachoma.6,9-12 Because of this concern, ALR is usually reserved for cases with mild-to-moderate entropic trichiasis without metaplastic lashes emanating from the posterior lamella.

The literature generally advises that ALR be modified and combined with other more complicated techniques for various phenotypes of trachomatous trichiasis.9 For instance, in cases of thickened tarsus, which is usually the case in TT patients, ALR should be combined with a tarsal wedge resection. For cases with lid retraction secondary to the scarred, shortened posterior lamella, ALR should be combined with dissection of the levator aponeurosis and Muller’s muscle, followed by advancing the tarso-conjunctiva.9 This individualized and tailored surgical approach may be suitable for highly skilled oculoplastic surgeons, but is not a practical strategy for nurses who manage a high volume of cases in trachoma-endemic settings. It would be difficult to tailor surgical procedures to the various stages of disease, given the current TT backlog that must be rapidly addressed to prevent ongoing incident visual impairment. Fortunately, the Ophthalmology paper and other studies of BLTR and PLTR have shown that these procedures are overall quite effective ‘one size fits all’ approaches that can be safely and effectively performed by trained non-physicians.  

While some physicians suggest refraining from making an incision in the posterior lamella, there is no evidence to support this stance. By contrast, there is strong evidence to indicate that surgical procedures involving the posterior lamella should be employe for severe cases of TT with metaplastic lashes and major lid shortening. Specifically, tarso-conjunctival rotation procedures, such as the PLTR, can provide adequate 180° rotation of the lid margin.9,13-15

Which surgery type is best?

A recent trial result comparing PLTR with BLTR shows that PLTR is more effective against the full spectrum of TT cases, with a lower rate of postoperative trichiasis among cases of varying severity. The findings suggest that PLTR is preferable for use in the programmatic management of varied phenotypes of TT, and where surgeries are performed by non-physician cadres with limited training.6 It is worth noting that TT recurrence, when encountered, is almost always minor (less than five lashes). This dramatically reduces the risk of corneal scarring and blindness from  trichiasis.  

In summary, the current literature indicates that tarsal rotation surgeries are superior to other approaches for the programmatic management of TT in trachoma-endemic settings. ALR has not been formally compared with tarsal rotation procedures, but is unlikely to be superior as it does not address the often-significant entropion caused by posterior lamella scarring.  


  1. Reacher M, Huber M, Canagaratnam R, Alghassany A. A trial of surgery for trichiasis of the upper lid from trachoma. British Journal of Ophthalmology 1990; 74(2): 109-13.
  2. Reacher M, Muñoz B, Alghassany A, et al. A controlled trial of surgery for trachomatous trichiasis of the upper lid. Archives of Ophthalmology 1992; 110(5): 667-74.
  3. Barr K, Essex RW, Liu S, Henderson T. Comparison of trichiasis recurrence after primary bilamellar tarsal rotation or anterior lamellar repositioning surgery performed for trachoma. Clinical and Experimental Ophthalmology 2014; 42(4): 311-6.
  4. Ahmed RA, Abdelbaky SH. Short Term Outcome of Anterior Lamellar Reposition in Treating Trachomatous Trichiasis. Journal of Ophthalmology 2015; 2015: 568363.
  5. Aghai GH, Gordiz A, Falavarjani KG, Kashkouli MB. Anterior lamellar recession, blepharoplasty, and supratarsal fixation for cicatricial upper eyelid entropion without lagophthalmos. Eye 2016; 30(4): 627-31.
  6. Habtamu E, Wondie T, Aweke S, et al. Posterior lamellar versus bilamellar tarsal rotation surgery for trachomatous trichiasis in Ethiopia: a randomised controlled trial. The Lancet Global Health 2016; 4(3): e175-e84.
  7. Rajak SN, Collin JR, Burton MJ. Trachomatous trichiasis and its management in endemic countries. Survey of ophthalmology 2012; 57(2): 105-35.
  8. Burton MJ, Habtamu E, Ho D, Gower EW. Interventions for trachoma trichiasis. Cochrane Database of Systematic Reviews 2015; (11): CD004008.
  9. Kemp EG, Collin JR. Surgical management of upper lid entropion. The British journal of ophthalmology 1986; 70(8): 575-9.
  10. Rajak SN, Habtamu E, Weiss HA, et al. The Clinical Phenotype of Trachomatous Trichiasis in Ethiopia: Not All Trichiasis Is Due to Entropion. Investigative Ophthalmology & Visual Science 2011; 52(11): 7974-80.
  11. Rajak SN, Habtamu E, Weiss HA, et al. Absorbable versus silk sutures for surgical treatment of trachomatous trichiasis in Ethiopia: a randomised controlled trial. PLoS medicine 2011; 8(12): e1001137.
  12. Rajak SN, Habtamu E, Weiss HA, et al. Surgery Versus Epilation for the Treatment of Minor Trichiasis in Ethiopia: A Randomised Controlled Noninferiority Trial. PLoS Med 2011; 8(12): e1001136.
  13. Waddell K. A new clamp for bilamellar tarsal rotation for trachomatous trichiasis. Community Eye Health 2009; 22(69): 13.
  14. Kettesy A. ON GENESIS AND OPERATION OF THE CICATRICIAL (TRACHOMATOUS) ENTROPION OF THE UPPER LID. The British journal of ophthalmology 1948; 32(7): 419-23.
  15. Nasr AM. Eyelid complications in trachoma. I. Cicatricial entropion. Ophthalmic surgery 1989; 20(11): 800-7.

Noninferiority trials confirm IOP benefits of once-daily latanoprostene bunod

FEB 06, 2018


This pooled analysis assessed the efficacy and safety of latanoprostene bunod compared with timolol for the treatment of open-angle glaucoma.

Study design

The authors analyzed data from two phase 3, randomized, multicenter, double-masked, parallel-group, noninferiority trials (APOLLO and LUNAR), comprising 840 participants. Adults with open-angle glaucoma or ocular hypertension were randomized 2:1 to receive once-daily latanoprostene bunod (0.024%) or twice-daily timolol (0.5%) for 3 months.


Patients on latanoprostene bunod achieved a significantly lower mean IOP compared with timolol patients at 9 evaluation time points throughout 3 months of follow-up. The latanoprostene arm also had a greater number of subjects that attained a mean IOP of ≤18 mm Hg and an IOP reduction of ≥25% from baseline.

The study detected a 5.9% rate of conjunctival hyperemia in the latanoprostene bunod group. Eye irritation and pain occurred in less than 5% of patients. There were no serious safety concerns.


The results might have been more clinically applicable if latanoprostene bunod had been compared with a prostaglandin analogue rather than timolol.

Clinical significance

This robust study confirms the efficacy of this novel ocular hypotensive agent, which was approved by the FDA in November 2017. Prior studies suggest that the agent may be more efficacious than prostaglandin analogues, which are currently considered first-line therapies. Further head-to-head trials comparing latanoprostene bunod with a prostaglandin therapy would help to elucidate which drug should be used as a first-line treatment.

Incidence of eyelid SCC appears to be rising

FEB 12, 2018


This retrospective study examined demographic risk factors for developing eyelid squamous cell carcinoma (SCC).

Study design

Using data from the National Cancer Registration and Analysis Service, investigators identified all cases of eyelid SCC in England between 2000 and 2014.


Over the 15-year study period, there were 4,022 patients with newly diagnosed SCC affecting the eyelid. The age-standardized number of reported cases of eyelid SCC rose approximately 2% per year over the study period.

The risk for developing an eyelid SCC approximately doubled each decade after age 60. Men were at 1.9-times greater relative risk compared with women. The authors did not find any association between income quintile and risk of SCC.


The cause for the increasing incidence of eyelid SCC was not studied. While age may represent one factor, others such as an increasing rate of patients receiving immunosuppression therapies may also play a role. The study did not look at environmental factors, which could also be a factor in the development of eyelid SCC.

Clinical significance

The incidence of eyelid SCC in England appears to be rising. Rates of eyelid SCC appear to rise with the increasing age of the population at approximately 2% per year. Risk approximately doubles each decade after age 60, and the risk is approximately twice as high for men compared with women.

Predicting postoperative refraction: Which formula is best?

This retrospective case series compared the accuracy of 7 popular IOL formulas for predicting postoperative refraction in eyes of all ocular dimensions

Study design

The analysis included 18,501 eyes receiving an Alcon monofocal IOL (SN60WF or SA60AT IOL) over an 18-month period. All eyes had biometry with the Lenstar 900 optical biometer.

Investigators analyzed the error in predicted spherical equivalent of each formula (Barrett Universal II, Haigis, Hoffer Q, Holladay 1, Holladay 2, Olsen, and SRK/T), including the Wang-Koch adjustment (Holladay 1, Hoffer Q, Haigis, SRK/T) for eyes with axial length longer than 25 mm.


For the SN60WF, the Barrett Universal II had the significantly lowest mean absolute error followed by the Olsen, Haigis 1, Holladay 1 Wang-Koch, Holladay 2, Holladay 1, Hoffer Q Wang-Koch, SRK/T, SRK/T Wang-Koch, Hoffer Q, and Haigis Wang-Koch. The results were similar for the SA60AT IOL.

For long eyes (>25.5mm), Olsen had the lowest mean error followed by Barrett, whereas Haigis Wang-Koch, Hoffer Q, and Holladay 1 were worst. For short eyes (<22.5mm), Barrett and Holladay 1 Wang-Koch were most accurate, and Hoffer Q, Holladay 2 and Hoffer Q Wang-Koch were least accurate.

Of note, all 7 formulas without the WK adjustment give results that within 0.1 D of predicted spherical equivalent for eyes with axial lengths between 23 and 25 mm. The major reason for the difference between the formulas is their performance outside this range.


These results may not apply to other IOL models and manufacturers. Due to a retrospectively optimized Haigis a0 constant and a large number of surgeons in the study (127 for SN60WF and 95 for SA60AT), the results may not hold true for individual surgeons. A significant number of patients (6,476) were excluded due to missing postoperative refractive information in the 2-week to 4-month postoperative period, possibly skewing results.

Clinical significance

Findings from this large study suggest the Barrett Universal II is the best overall formula, and had a high accuracy for both short and long eyes. The Hoffer Q was least accurate for short eyes. In general, applying the Wang-Koch modification of axial length for long eyes resulted in a shift from hyperopic to myopic outcomes.

Rho kinase inhibitor eyedrop demonstrates noninferiority to timolol

Investigators report findings from 2 noninferiority trials comparing once-daily netarsudil 0.02% (Rhopressa, Aerie) with twice-daily timolol 0.5% in patients with ocular hypertension or open-angle glaucoma.

Netarsudil is new class of glaucoma medication that inhibits Rho kinase and norepinephrine transporters. It lowers IOP by increasing trabecular outflow facility, decreasing production of aqueous humor and decreasing episcleral venous pressure.

Study design

After a wash-out phase, 1,167 patients in the ROCKET 1 and ROCKET 2 trials were randomized to once-daily netarsudil or twice-daily (BID) timolol. The ROCKET 2 trial had an additional nertasudil BID arm. Patients were followed through 3 months.


Netarsudil did not meet noninferiority criteria in the ROCKET 1 study (baseline washout IOP between 20 to 27 mm Hg). A post-hoc analysis revealed that netarsudil was noninferior to timolol for patients with a post-washout IOP lower than 25 mm Hg.

Each arm of the ROCKET-2 study included 122 patients with a baseline IOP lower than 25 mm Hg. The netarsudil arms (once-daily and twice-daily dosing) were both noninferior to once-daily timolol.

Conjunctival hyperemia was the most common adverse event in the netarsudil arms, and symptoms were usually mild. The high rate of conjunctival hyperemia (58.9%) with BID netarsudil among ROCKET-2 participants led to a 30% discontinuation rate, compared with a 10% to 12% drop-out rate with daily dosing.


The study population was redefined for a post-hoc analysis after completion of the ROCKET-1 study. It is not immediately clear why the narrowed range (post-washout baseline IOP between 20 to 25 mm Hg) met noninferiority criteria, while the higher baseline IOP (up to 27 mm Hg) did not.

Although timolol is the standard comparative drop for many glaucoma studies, prostaglandin analogues are now the usual first-line treatment for monotherapy and might have provided a more clinically meaningful comparison. Finally, this report only follows patients through 3 months. A longer follow-up period is desirable.

Clinical significance

Netarsudil was approved by the FDA in December 2017. It is exciting to have a potential glaucoma medication with a different mechanism of action in the armamentarium of ocular hypertensive medications.

While it seems unlikely that netarsudil would supplant prostaglandins for first-line monotherapy treatment, this drug could be a useful addition to the treatment regimen for patients with uncontrolled glaucoma. It is surprising that netarsudil failed to meet noninferiority criteria in the initial ROCKET-1 study population. Further studies with expanded inclusion criteria (baseline IOP up to 35 mm Hg) are underway.