What We Have Learned About Combining a Ketogenic Diet and Chemoimmunotherapy: a Case Report and Review of Literature.

Background: A high-fat, moderate-protein, low-carbohydrate ketogenic diet has been reported in the literature as a treatment option for patients with cancer. Case Presentation: A 69-year-old veteran was initially diagnosed with stage III colorectal cancer and progressed to having liver, pancreatic, and omental lymph node involvement despite completing adjuvant FOLFOX (fluorouracil, leucovorin calcium, and oxaliplatin) after surgery. The patient was treated with FOLFIRI (fluorouracil, leucovorin calcium, and irinotecan hydrochloride) and bevacizumab, followed by encorafenib and cetuximab on progression. Subsequently, he received pembrolizumab but continued to progress. The patient was later placed on trifluridine/tipiracil and bevacizumab concurrent with a ketogenic diet. Positron emission tomography and carcinoembryonic antigen levels indicated disease stabilization for 10 months. On progression, the patient was transitioned to ipilumimab and nivolumab and continued to adhere to the ketogenic diet. The patient's disease has continued to remain stable for the past 1 year. His degree of ketosis was determined using the glucose ketone index. The patient continues to have a good quality of life during concurrent ketogenic diet and therapy. Conclusions: This case supports the tolerability of the ketogenic diet along with chemotherapy and immunotherapy and should be considered as an adjunct to standard cancer treatment. In this report, we reviewed the latest literature about cellular mechanism of the ketogenic diet and the efficacy and relationship with chemotherapy and immunotherapy. We are about to open a ketogenic diet protocol at the Veterans Affairs Central California Health Care System in Fresno.

Dacryoscintigraphy as a guide for surgery in patients with functional epiphora.

OBJECTIVE: To investigate how dacryoscintigraphy (DSG) may benefit surgical planning for functional epiphora. METHODS: A retrospective multicenter case series was performed on patients with symptomatic tearing despite no identified external cause and normal lacrimal probing and irrigation (i.e., functional epiphora). All patients had preoperative DSG testing. Patients were excluded if DSG testing failed to detect a tear flow abnormality. Those with delayed tear flow prior to entering the lacrimal sac (presac) on DSG underwent surgery aimed at improving flow into the lacrimal sac. Those with delayed tear flow after the lacrimal sac (postsac) on DSG underwent dacryocystorhinostomy. Surgical success was defined as epiphora being completely resolved, significantly improved, or partially improved. Surgical failure was defined as epiphora being unchanged or worse than at the preoperative timepoint. RESULTS: A total of 77 cases (53 patients) of DSG-guided surgery were included. A presac delay was observed in 14 cases (18.2%) and post-sac delay in 63 (81.8%). Overall surgical success was 83.1% across the cohort. Success was 100% in the presac group and 79.4% in the postsac group (p = 0.06). Mean follow-up time was 22 months (SD = 21 months). CONCLUSION: A role was demonstrated for DSG in the planning of surgery for patients with functional epiphora. The DSG-guided approach, when compared with empirical lacrimal intubation or dacryocystorhinostomy, may be especially useful in cases of functional epiphora that are presac in nature.

Evaluating Measurement Properties of Patient-Reported Outcome Measures in Glaucoma: A Systematic Review.

TOPIC: The purpose of the current study was to systematically identify and evaluate existing patient-reported outcome measures (PROMs) for clinical glaucoma practice. CLINICAL RELEVANCE: Understanding and incorporating patient preferences into decision-making is now recognized as critical for optimal resource allocation, especially in technologically advancing areas, such as minimally invasive surgeries. Patient-reported outcome measures are instruments designed to evaluate the health outcomes that are most important to patients. Despite their recognized importance, especially in the era of patient-centered care, their routine use in clinical settings remains low. METHODS: A systematic literature search was conducted in 6 databases (EMBASE, MEDLINE, PsycINFO, Scopus, BIOSIS, and Web of Science) from the date of inception. Studies were included in the qualitative review if they reported measurement properties of PROMs in adult patients with glaucoma. COnsensus-based Standards for the selection of health Measurement INstruments guidelines were used to assess the included PROMs. The study protocol is registered with PROSPERO (registration number: CRD42020176064). RESULTS: The literature search yielded 2661 records. After deduplication, 1259 studies entered level 1 screening, and based on title and abstract review, 164 records proceeded to full-text screening. In 48 included studies, 70 instrument reports discuss 43 distinct instruments in 3 major categories: glaucoma-specific, vision-specific, and general health-related quality of life. Most used measures were glaucoma-specific (Glaucoma Quality of Life [GQL] and Glaucoma Symptom Scale [GSS]) and vision-specific (National Eye Institute Visual Function Questionnaire [NEI VFQ-25]). All 3 have sufficient validity (especially construct), with GQL and GSS having sufficient internal consistency, cross-cultural validity, and reliability, with reports suggesting high methodological quality. CONCLUSION: The GQL, GSS, and NEI VFQ-25 are the 3 most used questionnaires in a research setting, having considerable validation in a patient population with glaucoma. Limited reports on interpretability, responsiveness, and feasibility in all 43 identified instruments make identifying a single optimal questionnaire for clinical use challenging and highlight the need for further studies. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Prevalence and Predictors of Hering's Response in Müller's Muscle-conjunctival Resection.

PURPOSE: Determine the prevalence and predictors of Hering's response following Muller's muscle-conjunctival resection (MMCR). METHODS: Seventy-five consecutive patients undergoing unilateral MMCR were recruited in this prospective, multicenter, cohort study. Margin-reflex distance-1 (MRD1) of both eyelids was recorded preoperatively and postoperatively. One hundred forty-three variables were investigated as potential predictors of a late postoperative (≥3 months) Hering's response using regression analyses. Main outcome measures were Hering's response (≥0.5 mm descent of the unoperated eyelid from baseline), and a clinically relevant Hering's response (descent of the unoperated from baseline to a MRD1 ≤ 2.0 mm, or descent from baseline such that the MRD1 of the unoperated eyelid became >1 mm lower than the operated eyelid). RESULTS: Twenty-four (32.0%) patients had a late postoperative Hering's response, but only 6 (8.0%) responses were clinically relevant. A Hering's response at the immediate (OR 16.24, p = 0.02) and 1-week postoperative (OR 8.94, p = 0.04) timepoints predicted a late postoperative response. However, the presence (OR 7.84, p = 0.07) and amplitude (OR 8.13, p = 0.06) of a preoperative phenylephrine Hering's response did not predict a late postoperative response. Of the 10 patients with a clinically relevant phenylephrine Hering's response, only 1 demonstrated a clinically relevant response late postoperatively. CONCLUSION: Unilateral MMCR induces a clinically relevant Hering's response in 8% of patients. A preoperative phenylephrine Hering's response does not predict a late postoperative Hering's response. Therefore, when unilateral phenylephrine testing unmasks contralateral blepharoptosis, only the side with blepharoptosis at baseline should be operated.

Müller Muscle Conjunctival Resection: A Multicentered Prospective Analysis of Surgical Success.

PURPOSE: This is a multicenter prospective cohort study investigating Müller muscle conjunctival resection success rates based on marginal reflex distance-1 (MRD1) and symmetry criteria. A secondary objective was to identify predictors of success. METHODS: One hundred fifty-two patients with unilateral or bilateral blepharoptosis (229 eyelids) undergoing Müller muscle conjunctival resection were consecutively recruited from 2015 to 2020 at the Université de Montréal and University of California San Francisco. Ptosis was defined as MRD1 ≤ 2.0 mm or MRD1 > 1 mm lower than the contralateral eyelid. Patients were selected for Müller muscle conjunctival resection surgery if they demonstrated significant eyelid elevation following phenylephrine 2.5% testing. MRD1 success (operated eyelid achieving MRD1 ≥ 2.5 mm) and symmetry success (patient achieving an intereyelid MRD1 difference ≤ 1 mm) were evaluated for the patient cohort. Predictors of MRD1 and symmetry success were analyzed using multivariate regression analysis. RESULTS: MRD1 success was achieved in 72.1% (n = 165) of 229 operated eyelids. Symmetry success was achieved in 75.7% (n = 115) of 152 patients. MRD1 before phenylephrine testing was the only statistically significant predictor of MRD1 success (odds ratio [OR] 2.69, p = 0.001). Symmetry following phenylephrine testing was the only variable associated with increased odds of symmetry success (OR 2.71, p = 0.024), and unilateral surgery (OR 0.21, p = 0.004), the only variable associated with reduced odds of symmetry success. CONCLUSIONS: Müller muscle conjunctival resection effectively achieves postoperative MRD1 and symmetry success. MRD1 before phenylephrine testing is the strongest determinant of MRD1 success. Neither a large rise in MRD1 with phenylephrine nor increasing tissue resection length adequately counterbalance the effect of a low MRD1 before phenylephrine. Unilateral surgery and the absence of symmetry following phenylephrine predict greater odds of symmetry failure.

Ontario Cataract Quality Outcome Initiative: appropriateness and prioritization of cataract surgery.

OBJECTIVE: To explore the utility of the Catquest 9SF visual function (VF) questionnaire along with visual acuity (VA) for determining appropriateness and priority for cataract surgery. To evaluate the feasibility of administering the Catquest-9SF in a clinical setting using web-based electronic data capture and interpretation. DESIGN: Prospective multicentred interventional observational study. PARTICIPANTS: Subjects undergoing sequential cataract surgery in both eyes at 4 sites in Ontario. METHODS: We recorded best-corrected VA (BCVA) and VA with current correction (CCVA) in each eye and both eyes (OU) and Catquest-9SF responses on a tablet before and after cataract surgery. Linear regression models were employed to test for associations between VA and visual function (VF). RESULTS: Preoperative BCVA and CCVA in the worse eye were significant predictors of change in VF (p = 0.006 and p = 0.008, respectively); subjects with worse VA had a greater improvement in VF after surgery. There was a significant association between improvement in VF and improvement in CCVA OU (p = 0.001). Fourteen of 151 subjects (9%) had no improvement or worse VF scores after surgery. Within this group, 10 of 14 subjects had a preoperative score ≤-3, which is suggestive of minimal visual disability. Within this subset, 4 of 14 subjects (2.6%) had a preoperative BCVA of 20/30 or better in their worse eye. CONCLUSIONS: For patient groups with equal VA, the Catquest-9SF score can help determine priority for surgery. Web-based data capture and interpretation allow for efficient virtual assessments of VF. A BCVA in the worse eye of 20/30 or better combined with a Catquest-9SF score <-3 can be used as a guideline for lowest priority.

Public perception of laser-assisted blepharoplasty versus blade-assisted blepharoplasty.

OBJECTIVE: To evaluate perceptions of blade- versus laser-based blepharoplasty before and after being provided educational information. METHODS: This interventional pre-post study included 145 randomly selected participants (Maisonneuve-Rosemont Hospital, Montreal, Canada, August 2020) who were asked about their perceptions surrounding blepharoplasty. Participants then received information about the techniques before answering final questions. RESULTS: Participants perceived no difference in outcomes for blade (37%) versus laser (40%) blepharoplasty precounselling. This increased to laser blepharoplasty postintervention (56%, p < 0.001) despite being told that there was no difference in outcomes. The higher the level of education among participants, the more likely they were to correctly believe that both techniques had similar outcomes (p = 0.049). Most participants would choose laser blepharoplasty initially (64%), and this percentage increased postintervention (81%, p < 0.001). The preintervention perception of blade blepharoplasty recovery time (20.1 ± 32.6 days) was longer than that for laser blepharoplasty (13.5 ± 32.0 days, p = 0.01) and increased for both techniques postintervention (p < 0.001). Perceived pain was lower for laser blepharoplasty. Postintervention, participants responded that additional costs of ($975 ± $1,091) would justify laser over blade blepharoplasty. CONCLUSION: Elucidating patient perceptions and preferences for blade- versus laser-based blepharoplasty provides surgeons with perspective on how to tailor preoperative counselling. Before and after the intervention, participants had a bias toward choosing laser blepharoplasty. The intervention seems to falsely convince people that laser blepharoplasty leads to better outcomes. Because the doctor's advice can greatly impact patients' decisions, physicians have to be careful not to give false expectations when counselling patients. Inaccurate recall of key educational takeaways suggests that information should be vulgarized and delivered actively to patients.

Prospective evaluation of medical student accuracy conducting direct ophthalmoscopy with an unmodified iPhone X.

PURPOSE: To evaluate fundus examination accuracy of medical students when using an unmodified iPhone X or a direct ophthalmoscope in comparison to a staff ophthalmologist's retinal examination. METHODS: In this prospective comparative analysis, patients underwent dilated fundus examination by novice medical trainees using either an unmodified iPhone X or standard direct ophthalmoscope. The primary outcome was the mean difference and degree of agreement in cup-to-disc ratio between student examination and the staff ophthalmologist's cup-to-disc observation. RESULTS: A total of 18 medical students conducted 230 retinal examinations, 117 with the iPhone X and 113 with the direct ophthalmoscope. A greater proportion of students were unable to report cup-to-disc ratio using the iPhone X (81.2%) vs direct ophthalmoscope (30.1%). Student examination of cup-to-disc ratio led to a systematic bias (95% limits of agreement) of + 0.16 (-0.22 to + 0.54) and + 0.10 (-0.36 to + 0.56) with the iPhone X and direct ophthalmoscope, respectively. iPhone X and direct ophthalmoscope student observation concordance for optic disc colour (88.7 and 82.4%, respectively) and contour (68.3 and 74.2%, respectively) demonstrated low agreement with staff ophthalmologist findings. Student iPhone X observations demonstrated lower agreement with staff findings compared to direct ophthalmoscope observations for spontaneous venous pulsations (Cohen's Kappa = -0.044 vs 0.099). CONCLUSION: Amongst medical trainees, optic disc visualization using an unmodified iPhone X was inferior to the direct ophthalmoscope. When able to visualize the optic nerve head, there was no significant difference in reported cup-to-disc ratio between modalities. However, both modalities demonstrated poor reliability in comparison to staff ophthalmologist findings.

Rituximab-induced acute lympholysis and pancytopenia after COVID-19 vaccination.

Rituximab and COVID-19 vaccine can cause massive hyperacute depletion of B cells and plasma cells, as well as subsequent cytokine release syndrome, coagulopathy, and pancytopenia. These effects differ from the adverse effects that have been reported for rituximab, and new guidelines regarding the timing of rituximab infusion and vaccination are urgently needed.

Young and under the influence: A systematic literature review of the impact of cannabis on the driving performance of youth.

BACKGROUND: Young drivers ages 15-24 continue to constitute a high-risk population for fatal motor vehicle collisions (MVCs) compared to all other age groups. Driving under the influence of cannabis is an important contributor to the high rates of MVCs among youth. Understanding the specific impact of cannabis on the driving performance outcomes of young drivers can inform injury prevention, education, and intervention strategies. OBJECTIVES: This systematic literature review (SLR) aims to determine the Class (I- highest to IV-lowest) of evidence and level of confidence (A-high to U-insufficient) in the effects of cannabis on the driving performance of young drivers. METHODS: Registered in PROSPERO (#CRD42020180541), this SLR searched seven data bases and appraised the quality and confidence in the evidence using an established research methodology. RESULTS: Class II evidence suggests that THC is likely to reduce mean speed, headway distance, and reaction time; and increase lane and steering wheel position variability among young drivers (Level B, moderate confidence). CONCLUSIONS: This study shows that there is a moderate to low level of confidence on the impact of cannabis on the specific driving performance outcomes of young drivers. A need remains for Class I and II studies that focus on the specific effects on young drivers, distinguish between the biological and socially constructed variables of sex and gender, and includes larger and more representative samples.

Personal protective equipment (PPE) during the COVID-19 pandemic for oculofacial plastic and orbital surgery.

Purpose: To review the current literature on Coronavirus Disease 2019 (COVID-19) virology and transmission; to present a decision tree for risk stratifying oculofacial plastic and orbital surgeries; and to generate personal protective equipment (PPE) recommendations by risk category.Methods: A comprehensive literature review on COVID-19 was conducted. A two-stage modified Delphi technique involving 18 oculofacial plastic and orbital surgeons across Canada was used to determine consensus risk-stratification criteria and PPE recommendations for surgeries performed in the North American context.Results: COVID-19 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We summarize COVID-19 virology and transmission, as well as practice considerations for oculofacial plastic and orbital surgeons. Although SARS-CoV-2 is known to be transmitted predominantly by droplet mechanisms, some studies suggest that transmission is possible through aerosols. Among common procedures performed by oculofacial and plastic surgeons, some are likely to be considered aerosol-generating. Risk of transmission increases when manipulating structures known to harbor high viral loads. We present an algorithm for risk-stratification based on the nature of surgery and the anatomical sites involved and offer recommendations for PPE.Conclusions: Although universal droplet precautions are now recommended in most healthcare settings, some clinical situations require more stringent infection control measures. By highlighting high-risk scenarios specific to oculofacial plastic and orbital surgery, as well as PPE recommendations, we hope to enhance the safety of continued care during the COVID-19 pandemic.

Severe Intraoperative Orbital Venous Congestion during Resection of a Frontal Meningioma Presenting with Post-operative Vision Loss and Ophthalmoplegia: A Case Report.

We describe a unique case of a middle-aged man who noticed complete vision loss in the right eye after awaking from resection of a large right-sided frontal meningioma. Visual acuity was hand motions, and there were multiple signs of right orbital venous congestion. Magnetic resonance imaging and venography (MRI/V) of the brain and orbits demonstrated expected post-operative findings with no evidence of cavernous sinus thrombosis or fistula. Empiric treatment with intravenous antibiotics and intravenous methylprednisolone were ineffective. Immediate post-operative computerised tomography (CT) images were re-reviewed and revealed right restricted diffusion of the entire intraorbital right optic nerve. Discussion with the neurosurgical team revealed that during craniotomy, a prominent diploic venous plexus in the frontal bone adjacent to the meningioma was identified and coagulated with bone wax. Review of pre-operative imaging revealed large diploid flow voids in the right frontal bone, corresponding to the intraoperative findings. This prominent venous plexus appeared to drain from the meningioma posteriorly into the vein of Labbe. A second pathway drained anteriorly through the right angular vein into the orbit. We hypothesise that the posterior outflow pathway was coagulated intraoperatively, causing redirection of all venous outflow from the meningioma into the right orbit through the anterior pathway. This resulted in significant orbital hypertension with manifest signs and symptoms. Furthermore, sudden rise in intraorbital pressure led to infarction of the optic nerve, leaving the patient with hand motions vision. We suggest that pre-operative vascular imaging should be performed in patients with large meningiomas, as pre-operative embolisation of venous outflow channels may prevent severe post-operative complications.

Phacomorphic Angle-closure Following Silicone Oil Tamponade in a Pediatric Patient.

PURPOSE: The purpose of this study was to report a case of phacomorphic glaucoma following retinal detachment repair with silicone oil (SO) in a pediatric patient. STUDY DESIGN: Case report. METHODS: A chart review was conducted at St. Michael's Hospital and The Hospital for Sick Children (Toronto, Canada), where the patient received ophthalmic care from July 28, 2015 onwards. RESULTS: A 14-year-old boy with a history of traumatic retinal detachment and proliferative vitreoretinopathy in the left eye, requiring 2 pars plana vitrectomies, membrane peel, and SO tamponade, presented with 1-day history of decreased vision in the left eye, severe headache, nausea, and vomiting. Visual acuity was hand motions; intraocular pressure (IOP) was 54 mm Hg; the pupil was middilated and minimally reactive with a reverse relative afferent pupillary defect. Slit-lamp examination revealed an injected eye with diffuse microcystic corneal edema, a shallow anterior chamber (AC), and an intumescent cataract. Gonioscopy demonstrated closed angles in 3 quadrants. Compared with his last examination 6 weeks prior, where only a mild posterior subcapsular cataract was noted, the patient's presentation was suggestive of rapid lens intumescence causing acute angle-closure glaucoma. He was given topical and systemic treatment, including intravenous mannitol, and his IOP reduced to 22 mm Hg after 7 hours. Urgent lensectomy was performed the following day. Preoperative ultrasound biomicroscopy revealed a greatly increased lens thickness of 5.12 mm and an AC depth of 1.12 mm. The integrity of both anterior and posterior lens capsules was confirmed intraoperatively, and SO remained confined to the posterior segment. Postoperatively, the iris returned to a normal configuration with open angles, and IOP was 16 mm Hg with no antiglaucoma medications at the last follow-up. CONCLUSIONS: Acute angle-closure in children is a rare event. To our knowledge, this is the first reported case of phacomorphic glaucoma secondary to vitreoretinal surgery in the pediatric population. Although uncommon, ophthalmologists should be aware of this potential complication with the intraocular use of SO and administer urgent treatment accordingly.

Corneal Collagen Cross-Linking in the Management of Keratoconus in Canada: A Cost-Effectiveness Analysis.

PURPOSE: To use patient-level microsimulation models to evaluate the comparative cost-effectiveness of early corneal cross-linking (CXL) and conventional management with penetrating keratoplasty (PKP) when indicated in managing keratoconus in Canada. DESIGN: Cost-utility analysis using individual-based, state-transition microsimulation models. PARTICIPANTS: Simulated cohorts of 100 000 individuals with keratoconus who entered each treatment arm at 25 years of age. Fellow eyes were modeled separately. Simulated individuals lived up to a maximum of 110 years. METHODS: We developed 2 state-transition microsimulation models to reflect the natural history of keratoconus progression and the impact of conventional management with PKP versus CXL. We collected data from the published literature to inform model parameters. We used realistic parameters that maximized the potential costs and complications of CXL, while minimizing those associated with PKP. In each treatment arm, we allowed simulated individuals to move through health states in monthly cycles from diagnosis until death. MAIN OUTCOME MEASURES: For each treatment strategy, we calculated the total cost and number of quality-adjusted life years (QALYs) gained. Costs were measured in Canadian dollars. Costs and QALYs were discounted at 5%, converting future costs and QALYs into present values. We used an incremental cost-effectiveness ratio (ICER = difference in lifetime costs/difference in lifetime health outcomes) to compare the cost-effectiveness of CXL versus conventional management with PKP. RESULTS: Lifetime costs and QALYs for CXL were estimated to be Can$5530 (Can$4512, discounted) and 50.12 QALYs (16.42 QALYs, discounted). Lifetime costs and QALYs for conventional management with PKP were Can$2675 (Can$1508, discounted) and 48.93 QALYs (16.09 QALYs, discounted). The discounted ICER comparing CXL to conventional management was Can$9090/QALY gained. Sensitivity analyses revealed that in general, parameter variations did not influence the cost-effectiveness of CXL. CONCLUSIONS: CXL is cost-effective compared with conventional management with PKP in the treatment of keratoconus. Our ICER of Can$9090/QALY falls well below the range of Can$20 000 to Can$100 000/QALY and below US$50 000/QALY, thresholds generally used to evaluate the cost-effectiveness of health interventions in Canada and the United States. This study provides strong economic evidence for the cost-effectiveness of early CXL in keratoconus.