Carmen L. Oakley

A Comparative Cohort Study of Visual Outcomes in Femtosecond Laser-Assisted versus Phacoemulsification Cataract Surgery

PURPOSE To evaluate visual outcomes after femtosecond laser-assisted cataract surgery (LCS) with phacoemulsification cataract surgery (PCS). DESIGN Prospective, multicenter, comparative case series. PARTICIPANTS Consecutive patients undergoing femtosecond LCS or PCS with intraocular lens insertion. METHODS A total of 1876 eyes of 1238 patients (422 male and 772 female) who underwent cataract surgery between January 2012 and June 2014 were included in the study: 1017 eyes from center A and 859 eyes from center B. Cases underwent clinico-socioeconomic selection. Patients with absolute LCS contraindications were assigned to PCS; otherwise, all patients were offered LCS and elected on the basis of their decision to pay (the out-of-pocket cost for LCS). Demographic and postoperative data were collected to determine differences between groups. MAIN OUTCOME MEASURES Six-month postoperative visual and refractive outcomes. Masked subjective refractions were performed 2 to 6 months postoperatively. RESULTS There were 988 eyes in the LCS group and 888 eyes in the PCS group. Baseline best-corrected visual acuity (BCVA) was better in LCS compared with PCS (20/44.0 vs. 20/51.5; P < 0.0003). Preoperative surgical refractive aim differed significantly between groups (LCS -0.28 vs. PCS -0.23; P < 0.0001). More patients who received LCS had Toric lenses implanted compared with PCS (47.4% vs. 34.8%; P < 0.0001). Postoperative BCVA was better after LCS (20/24.5 vs. 20/26.4; P = 0.0003) with a greater proportion of LCS cases achieving BCVA >20/30 (LCS 89.7% vs. PCS 84.2%; P = 0.0006) and 20/40 (LCS 96.6% vs. PCS 93.9%; P = 0.0077). However, PCS cases had more letters gained compared with LCS cases (13.5 vs. 12.5 letters; P = 0.0088), reflecting baseline BCVA differences. Mean absolute error was higher in LCS compared with PCS (0.41 diopters [D] vs. 0.35 D; P < 0.0011). The percentage of eyes within 0.5 D of error from preoperative aim refraction was higher in the PCS group (LCS 72.2% vs. PCS 82.6%; P < 0.0001). CONCLUSIONS Femtosecond LCS did not demonstrate clinically meaningful improvements in visual outcomes over conventional PCS.

Demodex species in human ocular disease: new clinicopathological aspects

Demodex brevis and Demodex folliculorum are likely ubiquitous organisms associated with human eyelashes. However, they have also been implicated in the pathogenesis of external ocular diseases. This article reviews the current literature in regards to life cycle, morphology, pathogenesis and treatment of underlying Demodex spp. infestation and outlines the previously undescribed in vivo behaviour of the mites. Images were obtained from the epilation of lashes from 404 patients seen in clinical practice. Epilated lashes were placed on a microscope slide which had been coated with optically clear hypromellose/carbomer gel (Genteal gel, Novartis pharmaceuticals corporation, East Hanover, New Jersey). Adults were identified with either dark field or standard transmission microscopy at 40–100×. Eggs and other life-cycle stages were examined at 250× magnification, with transmission microscopy giving the best image resolution. The life cycle of the mite has been reviewed and simplified according to clinical observations. Clinical signs suggestive of underlying Demodex spp. infestation have been described, and their pathogenesis was explained based on the micrographic digital images obtained. The problem of symptomatic Demodex spp. disease likely reflects an imbalance in the external ocular ecology; however, the role of Demodex spp. as a commensal should not be overlooked. Treatment should not be aimed at total eradication of the mite but rather restoring the ocular ecology to a balanced state. By revisiting the life cycle of the mite, we can identify areas where possible intervention may be effective.

Visual outcomes with femtosecond laser-assisted cataract surgery versus conventional cataract surgery in toric IOL insertion

To evaluate the visual outcomes of femtosecond laser‐assisted cataract surgery (LCS) compared with phacoemulsification cataract surgery (PCS) in patients undergoing Toric IOL insertion.

Cystoid macular edema after femtosecond laser-assisted versus phacoemulsification cataract surgery.

Purpose To evaluate the incidence of postoperative clinical cystoid macular edema (CME) associated with femtosecond laser–assisted cataract surgery (Catalys laser system) versus phacoemulsification cataract surgery. Setting Launceston Eye Institute, Launceston, Tasmania, Australia. Design Nonrandomized, single‐surgeon, prospective, comparative cohort case series. Methods Patients who had femtosecond laser–assisted cataract surgery and phacoemulsification cataract surgery between March 2012 and July 2014 were included in the study. The femtosecond laser–assisted cataract surgery group had anterior capsulotomy, lens fragmentation, with or without corneal incisions via femtosecond laser pretreatment. Standard phacoemulsification surgery and foldable acrylic intraocular lens insertion proceeded in all cases. All patients received topical nonsteroidal drops commencing 2 days preoperatively and continuing for 4 weeks postoperatively. The incidence of postoperative clinical CME (confirmed by optical coherence tomography) and comparison between groups were measured. The main outcome measure was the clinical CME rates. Results Of the eyes, 833 had femtosecond laser–assisted cataract surgery amd 458 had standard phacoemulsification cataract surgery. Both groups had similar baseline parameters. There were 7 cases of postoperative CME (0.8%) in the femtosecond laser–assisted cataract surgery group compared to 1 case (0.2%) in the phacoemulsification cataract surgery group, highlighting a trend toward greater cystoid macular edema in the femtosecond laser–assisted cataract surgery group. This correlated with a change in laser treatment speed (due to a software upgrade), suggesting that retinal safety thresholds need further careful analysis. Conclusion Increased CME might be a subthreshold retinal injury safety signal after femtosecond laser pretreatment and warrants further study. Financial Disclosure There are no financial or conflicts of interest for any author.

Aqueous chlorhexidine (0.1%) is an effective alternative to povidone-iodine for intravitreal injection prophylaxis.

Editor, E ffective antisepsis along with strict aseptic technique (of drug and delivery) are recognized as the most important factors in the prevention of endophthalmitis associated with intravitreal injections (IVI). United States medicare data confirms an overall rate of about 0.1% for IVI-associated endophthalmitis (Schwartz & Flynn 2014), although many studies report lower rates (Dossarps et al. 2015). Povidone–iodine (5% aqueous) preparations have historically been considered the most effective antimicrobial prophylaxis for ophthalmic procedures and have been adopted as routine for IVI, although effective antisepsis has been demonstrated at lower concentrations, with 0.25% povidone–iodine a commonly used preparation in some countries (Berkelman et al. 1982; Shimada et al. 2013). Povidone–iodine has also previously been shown to be non-toxic to ocular tissues at concentrations up to 4%, with higher concentrations more likely to cause ocular surface side-effects (Trost et al. 2007). Postprocedure pain is a commonly recognized adverse event of IVI and has typically been attributed to chemical sensitivity (not allergy) to povidone–iodine on the ocular surface (especially concentrations of 5–10%). Aqueous chlorhexidine gluconate (0.1%) (see Fig. 1) has been described as an alternative antisepsis agent for IVI but has not been previously reported in published literature, and the label does caution against use ‘in irrigating eyes’. We report our own experience and rationale inusingaqueous chlorhexidine gluconate (0.1%Pfizer,NewYork) after incorporating it into exclusive use as antisepsis for IVI in two sites. All IVI were performed by a single surgeon in a dedicated procedure room with vinyl surfaces and HEPA-filtered air-conditioning system in keeping with RCOphth (UK) guidelines (Amaoku et al. 2009). After instilling a drop of topical anaesthesia (tetracaine), an initial drop of 0.1% chlorhexidine gluconate was instilled prior to lignocaine gel anaesthesia and the eye taped closed (10 mins). Following adequate anaesthesia time, the eye was irrigated with 0.1% chlorhexidine gluconate and a surgical drape applied. A further drop of chlorhexidine was instilled over the area marked for injection immediately prior to the injection. Aseptic technique (drug and needle) was observed at all times by both the ophthalmologist and assistant. There were a total of 4322 IVI performed between May 2013 and July 2015 using 0.1% chlorhexidine gluconate exclusively as antisepsis. There was one case of endophthalmitis, equating to a rate of 0.023%. This is comparable with the published rates of endophthalmitis with povidone–iodine preparations (Schwartz & Flynn 2014; Dossarps et al. 2015). The rationale for making a switch to aqueous 0.1% chlorhexidine gluconate came from our own patient surveillance of postprocedure pain scores on 121 patients undergoing intravitreal injection with povidone–iodine 5% preparation. Patients were asked to rank the pain they experienced on a scale of 0 to 10 with 0 representing no pain and 10 representing the worst possible pain. Of the 121 patients surveyed, 65% reported pain following the procedure and for 17% of patients this pain was reported as severe (eight of 10 or more). In an initial cohort (n = 20) of patients reporting high levels of pain, the antisepsis agent was switched to a 0.1% chlorhexidine gluconate preparation. The pain survey was continued, and we found a decrease in the average pain score from eight of 10 to three of 10. According to guidelines from the Center for Disease Control and Prevention, both chlorhexidine gluconate and povidone–iodine have a broad spectrum of activity; however, in regard to preoperative hand scrubs, chlorhexidine gluconate was superior in reducing skin microflora. Povidone–iodine is considered to provide intermediate level disinfection, while chlorhexidine gluconate is considered a low-level disinfectant (recommendations reflecting that limited studies exist for chlorhexidine in both efficacy and toxicity) (CDC 1999). There have previously been concerns about the safety of chlorhexidine for use in ophthalmic procedures, given the reported effect it can have on the corneal epithelium and corneal endothelium. However, aqueous chlorhexidine (gluconate) has been proven to be safe for ophthalmic use at concentrations of less than or equal to 1% (Hamill et al. 1984). Although literature on efficacy of chlorhexidine as an ophthalmic antiseptic preparation is limited, in vitro studies have been conducted looking at inhibition of bacterial growth on disc assays, as well as isolates of Staphylococcus epidermidis following irrigation of conjunctiva with various concentrations of chlorhexidine. This study found chlorhexidine has broad-spectrum action and effectively reduces bacterial counts when used as conjunctival irrigation, but requires longer contact time to achieve antisepsis (~2 min) (Hamill et al. 1984). There are some safety issues to consider in relation to the use of chlorhexidine as antisepsis for IVI. The use of chlorhexidine for irrigation of cutaneous wounds has previously been studied in a porcine model, and it was shown to delay re-epithelialization at a concentration of 0.2%; however, chlorhexidine was the only treatment to eradicate all bacteria at 48 h (Archer

Indwelling sub-tenon space catheter bupivicaine infusion for intractable ocular pain in secondary glaucoma refractory to medical management.

have been well described. Fluorescein angiography in two reported patients with MEK inhibitor-associated retinopathy has shown a lack of fluorescein leakage. The mechanism of MEK inhibitor maculopathy is poorly understood. Macular neurosensory retinal detachments have not been described in association with RAF inhibitors alone. Furthermore, ERK is more closely related to MEK in the MAPK pathway. Therefore, the complication described here was more likely secondary to the use of the ERK inhibitor rather than the pan-RAF inhibitor. However, we cannot exclude this as a possibility. The case presented here showed a greater degree of macular detachment than seen with patients in our institution with MEK inhibitor-associated retinopathy. To the best of our knowledge, there have been no previously published case reports in the literature describing bilateral neurosensory retinal detachment associated with ERK inhibitor use. However, one such case has been presented (Bakri SJ, American Society of Retina Specialists, Vancouver, July 2018).

Effect of intravitreal anti-vascular endothelial growth factor agents on blood pressure – a cross-sectional analysis

I ntravitreal injection with anti-vascular endothelial growth factor (VEGF) agents, such as ranibizumab (0.5 mg), bevacizumab (1.25 mg) and aflibercept (2mg), have the theoretical side effect of increasing blood pressure (BP) due to the their downstream effect of decreasing nitric oxide production, thereby inhibiting vasodilation and increasing vascular resistance [1]. When anti-VEGF agents are delivered intravenously, the incidence of new-onset hypertension is documented to be approximately 22.4%, compared with 8.3% for patients receiving placebo [2]. However, the effect of the relatively small doses delivered via the intravitreal route on long-term BP is unknown. Studies have shown that these small doses enter the systemic circulation; however, whether this translates into a clinical effect on BP is yet to be determined [3]. One recent study highlighted that the risk of hospitalization due to stroke or transient ischaemic attack in the month after treatment is higher in patients undergoing treatment with intravitreal ranibizumab; however, underlying issues with BP were not evaluated in the study [4]. The WHO defines the cut-off for safe SBP at 140 mmHg and DBP at 90mmHg [5]. Hypertensive emergency is defined as BP greater than 180 mmHg SBP and 120 mmHg DBP, with evidence of end organ damage. Hypertensive urgency is defined as the same elevation in BP, without evidence of end organ damage. Both are well documented to occur more frequently in patients with a history of hypertension when exposed to an additional inciting factor [6]. We performed a novel cross-sectional, observational study of patients undergoing long-term intravitreal antiVEGF injection for management of choroidal neovascular membrane due to age-related macular degeneration or cystoid macular oedema secondary to central retinal vein occlusion or diabetic retinopathy. Our aim was to highlight the rate of hypertension and hypertensive urgency amongst patients undergoing intravitreal injections with anti-VEGF agents. The first consecutive 251 patients receiving injections from January 2015 to August 2015 at a single centre were selected to participate in the study. Patients received intravitreal injections of ranibizumab, bevacizumab or aflibercept. Informed consent was obtained from the patients. Ethics approval was obtained through the University of Tasmania Human Research Ethics Committee (H1104344). Primary care physicians were contacted and asked to provide the patient’s baseline BP reading (prior to the first intravitreal injection). BP and pulse rate were measured prior to injection and 10min after injection. In addition, BP measurements were taken as patients presented for clinical review, on noninjection days. McNemar’s test was used to investigate the proportion of hypertensive patients (SBP> 140 mmHg or DBP 100 mmHg) at baseline, clinical review and injection. In our cohort, the mean age was 77 years (SD 10.1, range 33–97 years). A total of 251 patients (107 men and 144 women) were involved in the study. Baseline BP readings were collected for 123 patients, and random BP readings on a noninjection day were collected on 52 patients. Of the 251 patients, a total of 54 (22%) had a SBP reading greater than 180 mmHg on the day of the procedure. In addition, 198 (79%) patients were hypertensive (SBP> 140 mmHg) on the day of the procedure compared with 40 (33%) patients with baseline BP readings. Of the total cohort, 151 (60%) patients were diagnosed with preexisting hypertension and were being treated with antihypertensive medication by their primary care physician. Of the 100 patients without a preexisting diagnosis of hypertension, and therefore not on any antihypertensive medication, 72 (72%) had a SBP greater than 140 mmHg on the day of the procedure. There were 83 patients who were normotensive at baseline, with 64 (77%) of these hypertensive (>140 mmHg) on the day of procedure (P< 0.001). The data from our small cross-sectional study highlight that a significant percentage of patients undergoing intravitreal injections with anti-VEGF agents have SBP above the WHO-recommended safe BP level of 140mmHg. According to the Australian diabetes, obesity and lifestyle study conducted in 1999–2000, approximately 28% of people aged over 25 years in the general population within Australia were hypertensive (SBP> 140 mmHg) [7]. Although not directly comparable given our study cohort reflects an older population, our study nonetheless highlights that there are a significant number of patients being treated with anti-VEGF agents who are significantly hypertensive associated with their treatment. We found 79% of patients experienced elevated BP on the day of the procedure compared with 32% at baseline and 36% of patients with elevated BP at random BP readings. Interestingly, a similar proportion of patients without preexisting hypertension had elevated BP on the day of the procedure compared with patients with known preexisting hypertension. A large percentage of patients experience hypertensive urgency on the day of the procedure (22% on day of procedure compared with 8% for random BP reading and 1% prior to the initiation of anti-VEGF therapy). These episodes of dangerously high BP are most likely related to the anxiety associated with the procedure, rather than an effect of the drug. It has long been recognized that autonomic nervous system influences play a fundamental

Femtosecond laser assisted versus standard phacemulsification in toric intraocular lens insertion

We thank the authors, Levitz et al., for their interest in our paper regarding visual outcomes of toric intraocular lens (IOL) implantation in patients undergoing standard phaco-emulsification versus those undergoing additional femtosecond laser pretreatment. Our prospective real-world comparative studywas established in 2012, comparing femtosecond laser with standard phaco-emulsification, prior to publication of the sentinel references providedbyLevitz. Best-corrected visual acuity and letters gained were utilized as part of our study design, as no evidence existed demonstrating comparative safety or efficacy of femtosecond laser pretreatment with phaco-emulsification. Our toric IOL analysis represents a subset analysis from the overall prospective comparative cohorts rather than a studydesigned specifically to assess toric IOLs. We agree with Levitz et al. that 4years down the track, some of these study design measures as presented are too crude regarding providing a full assessment and interpretation of toric IOLs and the influence on themof Femtosecond laser. We are grateful therefore for Levitz et al., encouraging us to revisit our data, re-presenting in Table 1 relevant information, including refractive and uncorrected visual acuity results. As previously identified, there exists selection bias in our cohorts, but together, both cohorts represent all consecutive cataract cases presenting for surgery in a real-world unselected fashion. Our selection bias was firstly clinical, with ~5% of cases not considered suitable for femtosecond laser pretreatment (small pupil, corneal scarring, etc.), all of these (potentially more complicated) cases entering the phacoemulsification cohort. The remaining selection bias was socioeconomic, with all remaining (~95%) patients with cataract self-selecting either femtosecond laser pretreatment or phaco-emulsification based on their ability to pay for the additional femtosecond laser pretreatment procedure. We agree that it is unfortunate that our study design did not look inmore detail prospectively at differences in co-morbidities that may have arisen from such clinico-socioeconomic selection. To do so retrospectively though would be difficult and would introduce observer bias; consequently, we are left with speculation. We are mindful that our results can be interpreted in one of twoways: the Femtosecond laser protagonist seeing the outcome differences as evidence of Femtosecond laser benefit and the phaco-emulsification protagonist seeing the absence of pre-operative to post-operative change differences as evidence of a lack of benefit of femtosecond laser. We do not think that our study design is capable of definitively answering this question. Although we found a difference between cohorts in percentage patients achieving uncorrected visual acuity 6/12 or better, this difference persisted even with best correction (Table 1). Therefore, we think that the absence of significant refractive outcome differences between cohorts (residual cylinder [refractive astigmatism] and MAE) suggests that the answer lies more likely in baseline differences between cohorts (co-morbidities) rather than a real difference between the procedures in refractive outcomes (such as precision of capsulotomy or lens placement might afford from femtosecond laser). As such, we do not think that our results and discussion are incongruous, and based on our results, wedonot think that LCS canbe considered superior to PCS for visual outcomes in toric IOL surgeries. Our enthusiasm for this disruptive technology should be tempered by the lack of well-powered randomized controlled trial results showing significant benefit now 5years after femtosecond laser pretreatment for cataract surgery entering the mainstream marketplace.

Incidence of cystoid macular edema in femtosecond laser–assisted cataract surgery compared with manual cataract surgery

Incidence of cystoid macular edema in femtosecond laser–assisted cataract surgery compared with manual cataract surgery Levitz et al. recently published a paper comparing the rate of cystoid macular edema (CME) in patients having femtosecond laser–assisted cataract surgery versus standard phacoemulsification. In their realworld cohort, the overall rate of CME was approximately 1.0%, with no statistical difference between the femtosecond group and themanual group. The authors acknowledge the confounding bias of known CME risk factors; however, this does not allow exclusion of an independent effect of femtosecond laser–assisted cataract surgery on CME. There are additional sources of bias, which confound interpretation of this study’s results. First, data for the 2 cohorts were collected over different timeframes, with manual cases collected from January 2011 and femtosecond laser–assisted cataract surgery cases starting 18 months later (July 2012). Unfortunately, nobreakdownwasgiven for thenumber of manual cases performed to this timepoint or subsequent to femtosecond laser–assisted cataract surgery introduction. This is relevant because second, a different intervention (introduction of a topical nonsteroidal antiinflammatory drug [NSAID] use perioperatively) had occurred partway through the study period (June 2012). Moreover, the manuscript presents incongruous data despite indicating topical NSAID use occurred since June 2012; 6 cases (5 femtosecond laser–assisted cataract surgery and 1 manual) of CME are indicated following this date andwere listed in Table 1 as not having topical NSAID treatment perioperatively. Last, the manuscriptdoesnotmake clear theperioperativeprotocol with regard to the timing of commencement of topical NSAIDs and whether postoperative topical steroids were given in conjunction with topical NSAIDs. A CME rate of 1.0% would be considered high for patients receiving preoperative and postoperative topical NSAIDs combined with postoperative topical corticosteroids. Topical NSAIDs alone, although significantly better in protecting against CME than topical steroids alone (3.8% versus 25.3%), do not achieve prophylaxis comparable to combining agents. The timing of topical NSAID commencement is also relevant to its prophylaxis benefit. Randomized controlled trials have found that the incidence of CME is lower in patients treated with ketorolac commencing 3 days preoperatively and continuing postoperatively in conjunction with topical steroids compared with starting treatment on the day of surgery or no treatment at all. It is too early in the evolution of this technology to exclude an effect of femtosecond laser–assisted

Fifty-year follow-up and Strampelli anterior chamber intraocular lens

The Strampelli anterior chamber intraocular lens was created in 1953, and was primarily used to treat myopia and aphakia. Due to the positioning of the lens, it was associated with a number of complications, and was later modified to decrease the rate of significant complications, including endothelial cell loss. This paper describes a 62-year-old man, who has had a Strampelli intraocular lens (IOL) in situ for 52 years, with relatively few complications. The case provides a framework for reflection on the significant advances in the development of IOLs since the Strampelli era. The Strampelli anterior chamber intraocular lens was created in 1953, and was primarily used to treat myopia and aphakia. Due to the positioning of the lens, it was associated with a number of complications, and was later modified to decrease the rate of significant complications, including endothelial cell loss. This paper describes a 62-year-old man, who has had a Strampelli intraocular lens (IOL) in situ for 52 years, with relatively few complications. The case provides a framework for reflection on the significant advances in the development of IOLs since the Strampelli era.