Rotational stability of two different piggyback toric intraocular lenses for correction of high post-keratoplasty pseudophakic ametropia.

We present the case of a 65-year-old man with bilateral keratoconus and history of bilateral penetrating keratoplasty (PK) who developed gradual visual decline in the left eye due to cataract formation. Following successful left eye cataract surgery and monofocal, non-toric intraocular lens (IOL) in-the-bag implantation, the patient experienced persistently low uncorrected distance visual acuity (UDVA) due to high residual refractive error and intolerance to contact lenses. A supplementary toric IOL was placed in the ciliary sulcus, but subsequent rotational instability of the lens required repeated realignment. Despite two attempts at IOL repositioning, the rotational instability persisted, necessitating the replacement of the original Sulcoflex IOL with a toric, implantable Collamer lens. Following the implantation of the toric ICL, the patient achieved excellent UDVA with no adverse events over a 4-year follow-up period. This case highlights the potential rotational instability associated with toric piggyback IOLs in keratoconic, post-PK, pseudophakic eyes and the special considerations on choosing the type of piggyback lens in these eyes.

Clinical Characteristics and Outcomes of Fungal Keratitis in the United Kingdom 2011-2020: A 10-Year Study.

Fungal keratitis (FK) is a serious ocular infection that often poses significant diagnostic and therapeutic dilemmas. This study aimed to examine the causes, clinical characteristics, outcomes, and prognostic factors of FK in the UK. All culture-positive and culture-negative presumed FK (with complete data) that presented to Queen's Medical Centre, Nottingham, and the Queen Victoria Hospital, East Grinstead, between 2011 and 2020 were included. We included 117 patients (n = 117 eyes) with FK in this study. The mean age was 59.0 ± 19.6 years (range, 4-92 years) and 51.3% of patients were female. Fifty-three fungal isolates were identified from 52 (44.4%) culture-positive cases, with Candida spp. (33, 62.3%), Fusarium spp. (9, 17.0%), and Aspergillus spp. (5, 9.4%) being the most common organisms. Ocular surface disease (60, 51.3%), prior corneal surgery (44, 37.6%), and systemic immunosuppression (42, 35.9%) were the three most common risk factors. Hospitalisation for intensive treatment was required for 95 (81.2%) patients, with a duration of 18.9 ± 16.3 days. Sixty-six (56.4%) patients required additional surgical interventions for eradicating the infection. Emergency therapeutic/tectonic keratoplasty was performed in 29 (24.8%) cases, though 13 (44.8%) of them failed at final follow-up. The final corrected-distance-visual-acuity (CDVA) was 1.67 ± 1.08 logMAR. Multivariable logistic regression analyses demonstrated increased age, large infiltrate size (>3 mm), and poor presenting CDVA (<1.0 logMAR) as significant negative predictive factors for poor visual outcome (CDVA of <1.0 logMAR) and poor corneal healing (>60 days of healing time or occurrence of corneal perforation requiring emergency keratoplasty; all p < 0.05). In conclusion, FK represents a difficult-to-treat ocular infection that often results in poor visual outcomes, with a high need for surgical interventions. Innovative treatment strategies are urgently required to tackle this unmet need.

Dynamics of big bubble formation in deep anterior lamellar keratoplasty by the big bubble technique: in vitro studies.

PURPOSE: To examine the movement of air injected in the cornea in simulated deep anterior lamellar keratoplasty (DALK), from the needle tip to the formation of different types of big bubbles (BB) and to ascertain how air travels through the stroma and pre-Descemet's layer [Dua's layer (PDL)] to create a type-1 (air between PDL and deep stroma) and type-2BB (air between PDL and Descemet's membrane). METHODS: Air was injected in 57 sclerocorneal discs and the passage recorded. Leaking points and sites of commencement of type-1 and type-2BB were examined by scanning electron microscopy. Stromal distribution of air pockets was studied by light microscopy. Uninjected corneas served as controls. RESULTS: Injected air followed a consistent pattern, initially as radial tracks to the limbus, then as circumferential bands along the limbus and finally centripetally to create predominantly a type-1BB. Type-2BB started at the periphery, by air emerging through clusters of tiny fenestrations discovered in the periphery of PDL. Fifteen to 20 such clusters were also seen in control samples on either side of the Descemet's attachment. Type-1BB was formed by air emerging through wide spaces between lamellae of deep stroma. Histologically, the circumferential band revealed an aggregation of air pockets in the mid-stroma. CONCLUSION: The consistent pattern of passage of air is indicative of the architecture and microanatomy of the corneal stroma where collagen lamellae are orthogonally arranged centrally and as a circular annulus at the periphery. The novel peripheral fenestrations explain the peripheral commencement of a type-2BB and the escape of air into the anterior chamber during DALK.

Survival of corneal nerve/sheath structures in organ-cultured donor corneas.

PURPOSE: To study the morphology of human corneal nerves in eye bank organ-cultured corneas and in corneal grafts post-transplantation. METHODS: Thirty-seven organ-cultured corneas were divided into: Group-A, anterior 300-400 µm of 20 corneas used for Descemets stripping endothelial keratoplasty, and Group-B, 17 full-thickness corneas unsuitable for transplantation. Corneas whole mounts were stained for nerves using acetylcholinesterase technique and examined by NanoZoomer digital pathology microscope. Central and sub-Bowman's stromal nerves and the sub-basal nerve plexus including perforation sites and terminal bulbs were studied. Ten eyes were imaged following penetrating keratoplasty using in-vivo confocal microscopy (IVCM) for the presence of sub-basal and stromal nerves at 1, 4-5 and 7-8 weeks postoperatively (five eyes) and in all the other five eyes, the final follow-up was at 12 weeks. RESULTS: Fifteen of twenty (75%) corneas had stromal nerves in Group-A and 15 of 17 (88.2%) in Group-B. Average number of stromal nerves entering peripherally were 9.1 (range: 1-36). 7.5 in Group-A and 10.8 in Group-B. Central stromal nerves were seen in eight samples in Group-A and nine in Group-B. Many stromal nerves terminated abruptly without demonstrable continuity through Bowman's membrane. No terminal bulbs or sub-basal nerves were detected. In-vivo confocal microscopy (IVCM) showed 4 of 5 in 9 of 10 (90%) donor corneas had stromal nerves 1 week postoperatively, which remained present in 8 of 10 (80%) corneas at 4-5 weeks and in 9 of 10 (90%) at 7-8 weeks postoperatively. All 5 corneas analysed at 12 weeks showed the same stromal nerves from 1 to 12 weeks postoperatively. Sub-basal nerves were absent in all corneas over the 12-week study period. CONCLUSION: This study provides further insight into the behaviour of corneal nerves in transplanted corneas. Corneal stromal nerves/nerve-sheaths are preserved in organ-cultured eye bank eyes and persist post-transplantation up to 3 months. These could provide directional guidance to regenerating nerves from host stroma.

Amnion-assisted conjunctival epithelial redirection in limbal stem cell grafting.

AIMS: To develop a technique using amniotic membrane (AM) to prevent admixture of conjunctival epithelial cells and limbal explant-derived corneal epithelial cells in patients undergoing limbal stem cell transplantation. To compare this technique with the current method of 'sequential sector conjunctival epitheliectomy' (SSCE). METHODS: 26 patients with total limbal stem cell deficiency who underwent ocular surface reconstruction with limbal stem cells transplantation were retrospectively studied. Patients were categorised into group A (11) in which AM was used to direct the conjunctival epithelial cells away from the corneal surface so that the latter could be covered by the limbal explant-derived epithelial cells-the procedure was termed 'amnion-assisted conjunctival epithelial redirection' (ACER)-and group B (15) in which the conjunctival epithelium was prevented from migrating on to the corneal surface by SSCE. RESULTS: In nine eyes of group A, the conjunctival epithelium was successfully directed on to the AM, preventing admixture with limbal explant-derived corneal epithelial cells. The AM was removed or it came off spontaneously within 1-4 weeks. Patients treated with SSCE (group B) underwent two to four interventions until complete re-epithelialisation. 12 patients had pain or discomfort. 11 patients had conjunctival haemorrhage during SSCE. The cornea was epithelised from the limbal explant-derived epithelium in all patients. CONCLUSIONS: ACER is a viable option in limbal transplantation that reduces multiple patient visits, bleeding and pain that can be associated with SSCE.

Corneal hypoesthesia with normal sub-basal nerve density following surgery for trigeminal neuralgia.

PURPOSE: To evaluate the corneal sub-basal nerve plexus in patients presenting with hypoesthesia following surgery for trigeminal neuralgia. METHODS: Twenty-one patients who had unilateral medically uncontrolled trigeminal neuralgia and underwent ipsilateral surgery from 2006 to 2012 were included. Of these, 10 had microvascular decompression (MVD group) and 11 had balloon compression of the trigeminal ganglion (BC group). Slit lamp examination, Cochet-Bonnet aesthesiometery and in vivo confocal microscopy were carried out on both eyes of each patient. Nerve density data were statistically analysed. RESULTS: Corneal sensations and sub-basal nerve densities in MVD group were normal and equal in both the operated and unoperated sides, indicating that there was no intra-operative damage of the ophthalmic division of the trigeminal nerve (V1). However, those in BC group, despite having significantly reduced corneal sensations on the operated side (p = 0.007), did not demonstrate any significant difference in their sub-basal nerve densities (p = 0.477). No patient had any ocular symptoms. CONCLUSIONS: This study supports the hypothesis that complete ganglionic damage and/or postganglionic damage of V1 results in corneal hypoesthesia and neurotrophic keratitis, but partial ganglionic or preganglionic damage would preserve trophic function despite hypoesthesia and not result in clinically significant symptoms or signs of neurotrophic keratitis. The trophic and sensory functions of V1 are therefore independent and can be dissociated by disease or injury.

Big bubble deep anterior lamellar keratoplasty: the collagen layer in the wall of the big bubble is unique.

PURPOSE: In big bubble (BB), deep anterior lamellar keratoplasty intracorneal injection of air separates Descemet's membrane (DM) and the pre-Descemet's layer (Dua's layer [DL]) to create a type 1 BB. We tested the hypothesis that air injection after excision or ablation of DL will fail to produce a BB. METHODS: Nine human sclero-corneal discs were used. Three served as controls. In three, a type 1 BB was created, the bubble wall was excised and more air injected in an attempt to create another BB. In three samples, the DM was removed and 22µ of posterior cornea were ablated by phototherapeutic keratectomy (PTK). Air was injected to induce formation of a BB. Tissue from these experiments was subjected to light and electron microscopy. RESULTS: In all three control eyes, a type 1 BB (DL + DM) was obtained. Air injection after excision of the type 1 BB wall in three samples failed to produce another BB. Following PTK of DL, injection of air failed to create a BB in all three samples. Multiple points of air leak from the deep stroma were observed in all six samples. Light and electron microscopy showed a clear distinction between the ablated and non-ablated areas of cornea. CONCLUSIONS: This study supports the hypothesis that a BB cannot be created once the DL is excised or ablated. This adds to evidence that DL is unique. It also demonstrates that DL is not a random separation of deep stroma of the cornea.

Endothelial cell loss following tissue harvesting by pneumodissection for endothelial keratoplasty: an ex vivo study.

AIMS: To study ex vivo the difference in endothelial cell density (ECD) in tissue harvested by pneumodissection for pre-Descemet's endothelial keratoplasty (PDEK) and Descemet's membrane endothelial keratoplasty (DMEK). METHODS: Tissue for PDEK and DMEK were obtained from 10 eye bank sclerocorneal discs by trephination after air injection into corneal stroma and big bubble (BB) formation. PDEK tissue was prepared in five corneas after achieving a type 1 BB and DMEK after a type 2 BB in five corneas. Five sclerocorneal discs for each group were used as controls. Endothelial cell counts were obtained from all samples before and after injection using phase-contrast microscopy with an eyepiece reticle. We used paired t test to analyse the results using the GraphPad Prism V.6 software. RESULTS: The range of change of ECD before and after injection in the PDEK sample group varied from -9% to +0.2% with an average of -5.36% ±3.8%. The difference was not statistically significant (p=0.0512). On the other hand, the range of change of ECD of the DMEK groups before and after injection varied from -0.4 to -20.6, with an average of -12.44% ±8.11%. This difference was statistically significant (p=0.0456). Also, there was a significant difference between DMEK test samples (postinjection) and their controls (p=0.028). CONCLUSIONS: Corneal endothelial cell loss in PDEK tissue preparation is no worse, if not slightly better than, in DMEK tissue prepared by pneumodissection. PDEK preparation by pneumodissection represents a viable graft preparation technique.

Fine needle diathermy occlusion of corneal vessels.

AIMS: To evaluate the efficacy of fine needle diathermy (FND) occlusion of corneal vessels in relation to defined clinical indications. METHODS: A retrospective, consecutive case series including all patients treated by FND for occlusion of corneal vessels between 2004 and 2012. Indications were lipid keratopathy, preparation for keratoplasty to reduce risk of rejection and treatment of recalcitrant corneal graft rejection associated with stromal vessels. Our outcome measures were occlusion of corneal vessels with reduced corneal vascularisation, reduction in amount of lipid deposition, and reduction of graft rejection episodes. RESULTS: FND effectively reduced lipid deposition associated with the treated vessels in 14 out of 17 eyes (82.3%). When used to reduce corneal vascularisation before keratoplasty and to reduce intraoperative bleeding, the 1-year survival of the high-risk grafts was (84.6%). FND prevented further rejection episodes in 3 out of 4 corneal grafts. Fourteen eyes required retreatment (2-5 times) of which 9 had lipid keratopathy and 5 were in preparation for corneal grafting. CONCLUSIONS: FND is effective in occluding established corneal vessels. Corneal microperforation is a potentially serious adverse event, but other adverse events, such as striae, whitening and intracorneal haemorrhages are reversible. It should be considered for established corneal vessels, and can be combined with antivascular endothelial growth factors.

Collagen cross-linking with photoactivated riboflavin (PACK-CXL) for the treatment of advanced infectious keratitis with corneal melting.

PURPOSE: To investigate the efficacy and safety of corneal collagen cross-linking (CXL) with photoactivated riboflavin (photoactivated chromophore for infectious keratitis [PACK]-CXL) in the management of infectious keratitis with corneal melting. DESIGN: Prospective clinical trial. PARTICIPANTS: Forty eyes from 40 patients with advanced infectious keratitis and coexisting corneal melting. METHODS: Twenty-one patients (21 eyes) underwent PACK-CXL treatment in addition to antimicrobial therapy. The control group consisted of 19 patients (19 eyes) who received only antimicrobial therapy. MAIN OUTCOME MEASURES: The slit-lamp characteristics of the corneal ulceration, corrected distance visual acuity, duration until healing, and complications were documented in each group. The Mann-Whitney U test was used for statistical analysis. P values less than 0.05 were considered statistically significant. RESULTS: The average time until healing was 39.76 ± 18.22 days in the PACK-CXL group and 46.05 ± 27.44 days in the control group (P = 0.68). After treatment and healing, corrected distance visual acuity was 1.64 ± 0.62 in the PACK-CXL group and 1.67 ± 0.48 in the control group (P = 0.68). The corneal ulceration's width and length was significantly bigger in the PACK-CXL group (P = 0.004 and P = 0.007). Three patients in the control group demonstrated corneal perforation; infection recurred in 1 of them. No serious complications occurred in the PACK-CXL group. CONCLUSIONS: Corneal CXL with photoactivated riboflavin did not shorten the time to corneal healing; however, the complication rate was 21% in the control group, whereas there was no incidence of corneal perforation or recurrence of the infection in the PACK-CXL group. These results indicate that PACK-CXL may be an effective adjuvant therapy in the management of severe infectious keratitis associated with corneal melting.

The collagen matrix of the human trabecular meshwork is an extension of the novel pre-Descemet's layer (Dua's layer).

BACKGROUND: The trabecular meshwork (TM) located at the angle of the anterior chamber of the eye contributes to aqueous drainage. A novel layer in the posterior part of the human cornea has recently been reported (the pre-Descemet's layer (Dua's layer (PDL)). We examined the peripheral part of this layer in relation to the origin of the TM. METHODS: The PDL and TM of 19 human donor eyes and one exenterated sample were studied. Samples were examined by light and electron microscopy (EM) for tissue architecture and by immunohistology for four matricellular proteins, five collagen types and CD34. RESULTS: EM revealed that beams of collagen emerged from the periphery of PDL on the anterior surface of the Descemet's membrane and divided and subdivided to continue as the beams of the TM. Long-spacing collagen was seen in the PDL and TM. Trabecular cells (CD34-ve) associated with basement membrane were seen in the peripheral part of the PDL and corresponded to the start of the separation of the collagen lamellae of PDL. Collagen VI was present continuously in PDL and extended into the TM. Matricellular proteins were seen predominantly in the TM with only laminin extending into the periphery of PDL. CONCLUSIONS: This study provides an insight into the origins of the collagen core of the TM as an extension of the PDL of the cornea. This finding adds to the knowledge base of the TM and cornea and has the potential to impact future research into the TM and glaucoma.

Atypical hydrops in keratoconus.

To report the clinical presentation, progress and management of atypical acute hydrops. A retrospective case study of three patients with keratoconus, two of whom had previously undergone penetrating keratoplasty. The patients underwent full ophthalmological examination and digital slit-lamp imaging of the cornea throughout the course of the condition. The two patients who had previously undergone keratoplasty had spontaneous hydrops primarily affecting the host bed but in one case extended to the graft inferiorly; however, in the third patient it was traumatic in origin. The Descemet's tear affected the host rim in only one patient, which resolved spontaneously. In another patient, the hydrops was related to an internal dehiscence of the graft-host junction and had to be managed by an endothelial transplant covering the dehisced graft-host junction. In the third patient, hydrops secondary to trauma was also associated with acute haemops. Progression of keratoconus post keratoplasty can occur exclusively in the recipient bed leading to acute hydrops in the host sparing the transplanted cornea. The progressive thinning and ectasia of the recipient bed can also result in internal graft-host dehiscence leading to chronic oedema. Rapid entry of aqueous or blood cells into the corneal stroma following acute rupture of the Descemet's membrane suggests that the abnormal stroma of the eye with keratoconus may have an important role to play in the pathogenesis of acute hydrops/haemops.